SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

SCOTTSDALE, ARIZ. – Serum vitamin D level was not significantly associated with atopic dermatitis or disease severity in a single-center study of more than 600 children and adolescents.

However, “we did observe a strong correlation between average serum vitamin D levels and skin type, as well as body mass index,” said Kavita Darji, a medical student at Saint Louis (Mo.) University, who presented the findings in a poster at the annual meeting of the Society for Investigative Dermatology. Those findings challenge the logic of following universal definitions of vitamin D deficiency, especially given the phenotypic heterogeneity of patients in the United States, she added in an interview.

Amy Karon/Frontline Medical News

Serum vitamin D testing is one of most common laboratory assays in this country, but clinicians still debate the risks and benefits of supplementing children and adolescents who test below the Endocrine Society’s threshold for sufficiency (30.0 ng/mL).

To identify factors affecting vitamin D levels, Ms. Darji and her associates reviewed electronic medical charts for patients under age 22 years at Saint Louis University medical centers between 2009 and 2014. The cohort of 655 patients was primarily white (64%) or black (29%), and was nearly equally balanced by gender; their average age was 10 years. The researchers analyzed only the first vitamin D serum measurement for each patient, and defined deficiency as a level under 20 ng/mL, insufficiency as a level between 20 and 29.9 ng/mL, and sufficiency as a level of at least 30 ng/mL.

Serum vitamin D levels were slightly lower among atopic patients, compared with those without atopy, but the difference did not reach statistical significance (about 25 ng/mL vs. about 38 ng/mL; P greater than .05). “We also did not find an association between AD severity and vitamin D level,” Ms. Darji reported. Instead, race and body mass index were the most significant predictors of vitamin D deficiency, probably because these factors directly affect cutaneous photo-induced vitamin D synthesis and the sequestration of fat-soluble vitamins in adipose tissue, she said.

Using the standard definitions, more than 50% of black patients were vitamin D deficient, while less than 30% had sufficient vitamin D levels. In contrast, about 25% of white patients were vitamin D deficient, while nearly 40% had sufficient vitamin D levels (P less than .0001 for proportions of deficiency by race). Furthermore, only about 10% of obese children (those who exceeded the 99th percentile of BMI for age) had sufficient vitamin D levels, compared with more than 40% of underweight children and about 30% of normal-weight children (P less than .00001).

Since vitamin D deficiency was more common among black and obese patients, “maybe they could benefit from a different cut-off value than the standard 30 ng per mL that we used,” Ms. Darji said. “The question is, do they really require these supplements? It may be beneficial to look at the unique characteristics of each patient before supplementing, because the risks of supplementation are considerable in terms of bone health and cardiovascular disease.”

Vitamin D levels did not vary significantly by gender or by month or season measured, Ms. Darji noted. She reported no funding sources and had no disclosures.

While most Americans were still reacting in horror and disbelief to news of a mass shooting at the Pulse nightclub in Orlando, Florida in the early morning hours of June 12, 2016, the thoughts of most emergency physicians (EPs) were probably focused on the ongoing efforts to save as many victims as possible: What was the closest Level 1 trauma center, and how deep was the ED staffing there that night? Was there a need for additional resources, and perhaps even, could they get there in time to help? In this issue of Emergency Medicine (EM), Residency Program Director Salvatore Silvestri, MD, and his emergency medicine colleagues masterfully recount events from that night as they unfolded, both at the scene and two blocks away at the Orlando Regional Medical Center (ORMC) ED, in the minutes and hours following the first reported shootings.

Being prepared for a mass-casualty incident (MCI) is an extraordinarily expensive requirement of a hospital: It must acquire and maintain adequate resources and communication capabilities; periodically perform unannounced drills that disrupt other hospital activities; and ensure that all EPs and staff are not only able to perform their own day-to-day roles as attending physicians, residents, nurses, etc, but are also capable of taking on even greater responsibilities during an MCI—depending on the day and time it occurs. As you will read in the pages that follow, in the early morning hours of June 12, many of the practiced exercises and rehearsed procedures proved useful, even life-saving, while others had to be discarded or ignored in favor of improvised solutions to rapidly transport and treat the large number of victims with unanticipated needs, under unique conditions. 

In any MCI, saving the largest number of victims invariably depends on rapidly instituting some deviations from standard operating procedures (SOPs) and standards of care (SOCs). As described by the ORMC EP authors, “...law enforcement vehicles and ambulances would make the two-block drive from the scene to ORMC carrying as many patients as they safely could, and return immediately after offload….minimal interventions were performed and unlike standard procedure, EMS could offer no prearrival report to the hospital.”

Deviations from SOPs and SOCs during an MCI are not confined to prehospital care, but often extend into the ED and beyond. Most difficult for an EP participating in an MCI is the moment of realization that the sheer number of seriously injured and dying patients arriving en masse mandates a change from “ED triage” to “battlefield triage.” As Dr Ponder recalled, “One of the first few patients I saw was pulse­less, and as I went to start chest compressions, I was stopped by a trauma surgeon who said, ‘He’s gone, focus on the ones we can help.’”

In EDs, dying patients are attended to first with extensive staff and resources, while, as a result, less seriously ill patients must sometimes wait longer for care. The opposite is true on the battlefield, where near-death victims of lethal injuries are provided only with comfort care, at most, in order to save those who have a chance of surviving their extensive or serious injuries. 

For hospitals and staff, the costs incurred by disaster preparedness are great and invariably exceed government funding provided for these efforts, but how much greater would be the human toll from an MCI without such efforts? All EPs should be proud of what our colleagues at ORMC accomplished on June 12. Though most EPs may never have to deal directly with an MCI, the Orlando nightclub shooting incident was only one of the latest MCIs, certainly not one of the last.

Previous editorials on MCIs may be found in EM September 2006 (9/11), June 2011 (first responders), September 2011 (9/11), November 2011 (surge capacity), and September 2012 (surge capacity/Hurricane Sandy).

While most Americans were still reacting in horror and disbelief to news of a mass shooting at the Pulse nightclub in Orlando, Florida in the early morning hours of June 12, 2016, the thoughts of most emergency physicians (EPs) were probably focused on the ongoing efforts to save as many victims as possible: What was the closest Level 1 trauma center, and how deep was the ED staffing there that night? Was there a need for additional resources, and perhaps even, could they get there in time to help? In this issue of Emergency Medicine (EM), Residency Program Director Salvatore Silvestri, MD, and his emergency medicine colleagues masterfully recount events from that night as they unfolded, both at the scene and two blocks away at the Orlando Regional Medical Center (ORMC) ED, in the minutes and hours following the first reported shootings.

Being prepared for a mass-casualty incident (MCI) is an extraordinarily expensive requirement of a hospital: It must acquire and maintain adequate resources and communication capabilities; periodically perform unannounced drills that disrupt other hospital activities; and ensure that all EPs and staff are not only able to perform their own day-to-day roles as attending physicians, residents, nurses, etc, but are also capable of taking on even greater responsibilities during an MCI—depending on the day and time it occurs. As you will read in the pages that follow, in the early morning hours of June 12, many of the practiced exercises and rehearsed procedures proved useful, even life-saving, while others had to be discarded or ignored in favor of improvised solutions to rapidly transport and treat the large number of victims with unanticipated needs, under unique conditions. 

In any MCI, saving the largest number of victims invariably depends on rapidly instituting some deviations from standard operating procedures (SOPs) and standards of care (SOCs). As described by the ORMC EP authors, “...law enforcement vehicles and ambulances would make the two-block drive from the scene to ORMC carrying as many patients as they safely could, and return immediately after offload….minimal interventions were performed and unlike standard procedure, EMS could offer no prearrival report to the hospital.”

Deviations from SOPs and SOCs during an MCI are not confined to prehospital care, but often extend into the ED and beyond. Most difficult for an EP participating in an MCI is the moment of realization that the sheer number of seriously injured and dying patients arriving en masse mandates a change from “ED triage” to “battlefield triage.” As Dr Ponder recalled, “One of the first few patients I saw was pulse­less, and as I went to start chest compressions, I was stopped by a trauma surgeon who said, ‘He’s gone, focus on the ones we can help.’”

In EDs, dying patients are attended to first with extensive staff and resources, while, as a result, less seriously ill patients must sometimes wait longer for care. The opposite is true on the battlefield, where near-death victims of lethal injuries are provided only with comfort care, at most, in order to save those who have a chance of surviving their extensive or serious injuries. 

For hospitals and staff, the costs incurred by disaster preparedness are great and invariably exceed government funding provided for these efforts, but how much greater would be the human toll from an MCI without such efforts? All EPs should be proud of what our colleagues at ORMC accomplished on June 12. Though most EPs may never have to deal directly with an MCI, the Orlando nightclub shooting incident was only one of the latest MCIs, certainly not one of the last.

Previous editorials on MCIs may be found in EM September 2006 (9/11), June 2011 (first responders), September 2011 (9/11), November 2011 (surge capacity), and September 2012 (surge capacity/Hurricane Sandy).

While most Americans were still reacting in horror and disbelief to news of a mass shooting at the Pulse nightclub in Orlando, Florida in the early morning hours of June 12, 2016, the thoughts of most emergency physicians (EPs) were probably focused on the ongoing efforts to save as many victims as possible: What was the closest Level 1 trauma center, and how deep was the ED staffing there that night? Was there a need for additional resources, and perhaps even, could they get there in time to help? In this issue of Emergency Medicine (EM), Residency Program Director Salvatore Silvestri, MD, and his emergency medicine colleagues masterfully recount events from that night as they unfolded, both at the scene and two blocks away at the Orlando Regional Medical Center (ORMC) ED, in the minutes and hours following the first reported shootings.

Being prepared for a mass-casualty incident (MCI) is an extraordinarily expensive requirement of a hospital: It must acquire and maintain adequate resources and communication capabilities; periodically perform unannounced drills that disrupt other hospital activities; and ensure that all EPs and staff are not only able to perform their own day-to-day roles as attending physicians, residents, nurses, etc, but are also capable of taking on even greater responsibilities during an MCI—depending on the day and time it occurs. As you will read in the pages that follow, in the early morning hours of June 12, many of the practiced exercises and rehearsed procedures proved useful, even life-saving, while others had to be discarded or ignored in favor of improvised solutions to rapidly transport and treat the large number of victims with unanticipated needs, under unique conditions. 

In any MCI, saving the largest number of victims invariably depends on rapidly instituting some deviations from standard operating procedures (SOPs) and standards of care (SOCs). As described by the ORMC EP authors, “...law enforcement vehicles and ambulances would make the two-block drive from the scene to ORMC carrying as many patients as they safely could, and return immediately after offload….minimal interventions were performed and unlike standard procedure, EMS could offer no prearrival report to the hospital.”

Deviations from SOPs and SOCs during an MCI are not confined to prehospital care, but often extend into the ED and beyond. Most difficult for an EP participating in an MCI is the moment of realization that the sheer number of seriously injured and dying patients arriving en masse mandates a change from “ED triage” to “battlefield triage.” As Dr Ponder recalled, “One of the first few patients I saw was pulse­less, and as I went to start chest compressions, I was stopped by a trauma surgeon who said, ‘He’s gone, focus on the ones we can help.’”

In EDs, dying patients are attended to first with extensive staff and resources, while, as a result, less seriously ill patients must sometimes wait longer for care. The opposite is true on the battlefield, where near-death victims of lethal injuries are provided only with comfort care, at most, in order to save those who have a chance of surviving their extensive or serious injuries. 

For hospitals and staff, the costs incurred by disaster preparedness are great and invariably exceed government funding provided for these efforts, but how much greater would be the human toll from an MCI without such efforts? All EPs should be proud of what our colleagues at ORMC accomplished on June 12. Though most EPs may never have to deal directly with an MCI, the Orlando nightclub shooting incident was only one of the latest MCIs, certainly not one of the last.

Previous editorials on MCIs may be found in EM September 2006 (9/11), June 2011 (first responders), September 2011 (9/11), November 2011 (surge capacity), and September 2012 (surge capacity/Hurricane Sandy).

Dr. Catalina Matiz and David Ginsberg describe the diagnosis and treatment of discoid lupus erythematosus in children.

Discoid lupus erythematosus

Discoid lupus erythematosus (DLE) is a relatively common form of chronic cutaneous lupus, although its presentation in children is rare. The typical presentation of DLE is well-circumscribed, indurated, sometimes scaly round or oval plaques with pigmentary change, often red to purple in color. DLE also is clinically associated with telangiectasia, scarring, and follicular plugging, which has a characteristic appearance of “carpet tacking” beneath the scale.

When left untreated, these lesions may result in areas of long-term hypo- or hyperpigmentation, as well as atrophy and scarring.1 These cutaneous manifestations often are exacerbated by UV light exposure. This is particularly problematic because DLE most often affects the face, although lesions also can be found on the scalp, ears, trunk, extremities, and in the mouth as well.

Currently, there are few studies looking specifically at DLE in children and, based on the studies that have been done, there appear to be several important differences between the adult and pediatric populations. DLE affects women more than twice as much as men in the adult population, but reports vary as to whether this female predominance carries over to affected children.^2,3 Adults with DLE rarely have a family history of systemic lupus erythematosus (SLE), with rates reported between 1% and 4.4%. In children, however, the reported rates of family history increase tenfold to 11%-40%.²

One study showed that children with DLE progress to SLE at a rate of 23.5%-26%, which is higher than reported rates in adults of 5%-20%.^2,4 For this reason, repeated laboratory studies are essential in the follow-up of children diagnosed with DLE, given the possibility of a transition to systemic disease, particularly within the first year of diagnosis. Disseminated lesions can be a red flag for future progression to SLE.²

Differential diagnosis

The differential diagnosis of infiltrated annular lesions on the face and ears should include conditions such as tinea faciae, seborrheic dermatitis, granuloma annulare, cutaneous lymphoma, sarcoidosis, and leishmaniasis. When the lesions are present on the ear or nose, as in the case of this patient, relapsing polychonritis also may be considered.

Although histology plays a large part in diagnosing DLE, clinical presentation and recognizing the need for a biopsy are important.⁵ Tinea faciei, a fungal infection of the face, can present as erythematous scaly plaques.⁶ A thorough history and physical exam are important in differentiating tinea faciei from DLE because the former often begins as a small scaly papule that annularly expands outward to form larger plaque with scale around the outer rim, as opposed to DLE, which may have an adherent scale across the entire plaque.⁵ A potassium hydroxide (KOH) preparation of scraped scale from one of the lesions or a fungal culture can confirm the diagnosis of tinea faciei.⁶

Seborrheic dermatitis can be localized to the face and scalp and presents with greasy yellow scales. Early lesions of DLE can be difficult to differentiate from seborrheic dermatitis.

Infiltrated annular lesions on the face may represent granulomatous conditions such as granuloma annulare or sarcoidosis, but these lesions usually lack the presence of scale that can be seen in DLE.

Relapsing polychondritis presents as intermittent episodes of cartilage inflammation, usually affecting the cartilage of the ear, nose, and respiratory tract. Areas affected do not show changes on the surface of the skin as it occurs in DLE lesions.

As mentioned above, family history of SLE could indicate a potential for DLE in a small percentage of patients, but the clinical feature of the scaly plaques with the carpet tacking underneath the scale, caused by follicular plugging, is helpful in making the diagnosis clinically. Ultimately, the best way to differentiate anything resembling DLE is through histology and direct immunofluorescence (DIF). Histologic findings in DLE include epidermal atrophy, basal membrane cell vacuolization, hyperkeratosis, parakeratosis, corneal plugs, pseudoscysts, and acanthosis.³ The lupus band test is done using DIF and is a widely used tool for making the diagnosis of DLE based on the distribution of immunoglobulin deposition in the basement membrane zone.⁷

Treatment

Without timely diagnosis and treatment of DLE, the lesions can progress to scarring and atrophy, leading to a decreased quality of life. UV light exposure and smoking can exacerbate DLE, so sun protection and smoking cessation are both recommended in patients with DLE, although, admittedly, the latter is less relevant in the pediatric population.¹ Topical, intralesional, or systemic corticosteroids, with or without antimalarials, are the first line therapy for the management of DLE.¹ For refractory cases, some reports document the use of topical calcineurin inhibitors, dapsone, methotrexate, and topical or systemic retinoids.¹ For severe cases, intravenous immunoglobulin, ustekinumab, and rituximab also may be used.¹

References

1. Dermatol Ther. 2016 Apr 12 Epub.
2. Pediatr Dermatol. 2008 Mar-Apr;25(2):163-7.
3. Pediatr Dermatol. 2003 Mar-Apr;20(2):103-7.
4. J Am Acad Dermatol. 2015 Apr;72(4):628-33.
5. Pediatr Dermatol. 2016 Mar-Apr;33(2):200-8.
6. Pediatr Clin North Am. 2014 Apr;61(2):443-55.
7. Am J Dermatopathol. 2016 Feb;38(2):121-3.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg describe the diagnosis and treatment of discoid lupus erythematosus in children.

Discoid lupus erythematosus

Discoid lupus erythematosus (DLE) is a relatively common form of chronic cutaneous lupus, although its presentation in children is rare. The typical presentation of DLE is well-circumscribed, indurated, sometimes scaly round or oval plaques with pigmentary change, often red to purple in color. DLE also is clinically associated with telangiectasia, scarring, and follicular plugging, which has a characteristic appearance of “carpet tacking” beneath the scale.

When left untreated, these lesions may result in areas of long-term hypo- or hyperpigmentation, as well as atrophy and scarring.1 These cutaneous manifestations often are exacerbated by UV light exposure. This is particularly problematic because DLE most often affects the face, although lesions also can be found on the scalp, ears, trunk, extremities, and in the mouth as well.

Currently, there are few studies looking specifically at DLE in children and, based on the studies that have been done, there appear to be several important differences between the adult and pediatric populations. DLE affects women more than twice as much as men in the adult population, but reports vary as to whether this female predominance carries over to affected children.^2,3 Adults with DLE rarely have a family history of systemic lupus erythematosus (SLE), with rates reported between 1% and 4.4%. In children, however, the reported rates of family history increase tenfold to 11%-40%.²

One study showed that children with DLE progress to SLE at a rate of 23.5%-26%, which is higher than reported rates in adults of 5%-20%.^2,4 For this reason, repeated laboratory studies are essential in the follow-up of children diagnosed with DLE, given the possibility of a transition to systemic disease, particularly within the first year of diagnosis. Disseminated lesions can be a red flag for future progression to SLE.²

Differential diagnosis

The differential diagnosis of infiltrated annular lesions on the face and ears should include conditions such as tinea faciae, seborrheic dermatitis, granuloma annulare, cutaneous lymphoma, sarcoidosis, and leishmaniasis. When the lesions are present on the ear or nose, as in the case of this patient, relapsing polychonritis also may be considered.

Although histology plays a large part in diagnosing DLE, clinical presentation and recognizing the need for a biopsy are important.⁵ Tinea faciei, a fungal infection of the face, can present as erythematous scaly plaques.⁶ A thorough history and physical exam are important in differentiating tinea faciei from DLE because the former often begins as a small scaly papule that annularly expands outward to form larger plaque with scale around the outer rim, as opposed to DLE, which may have an adherent scale across the entire plaque.⁵ A potassium hydroxide (KOH) preparation of scraped scale from one of the lesions or a fungal culture can confirm the diagnosis of tinea faciei.⁶

Seborrheic dermatitis can be localized to the face and scalp and presents with greasy yellow scales. Early lesions of DLE can be difficult to differentiate from seborrheic dermatitis.

Infiltrated annular lesions on the face may represent granulomatous conditions such as granuloma annulare or sarcoidosis, but these lesions usually lack the presence of scale that can be seen in DLE.

Relapsing polychondritis presents as intermittent episodes of cartilage inflammation, usually affecting the cartilage of the ear, nose, and respiratory tract. Areas affected do not show changes on the surface of the skin as it occurs in DLE lesions.

As mentioned above, family history of SLE could indicate a potential for DLE in a small percentage of patients, but the clinical feature of the scaly plaques with the carpet tacking underneath the scale, caused by follicular plugging, is helpful in making the diagnosis clinically. Ultimately, the best way to differentiate anything resembling DLE is through histology and direct immunofluorescence (DIF). Histologic findings in DLE include epidermal atrophy, basal membrane cell vacuolization, hyperkeratosis, parakeratosis, corneal plugs, pseudoscysts, and acanthosis.³ The lupus band test is done using DIF and is a widely used tool for making the diagnosis of DLE based on the distribution of immunoglobulin deposition in the basement membrane zone.⁷

Treatment

Without timely diagnosis and treatment of DLE, the lesions can progress to scarring and atrophy, leading to a decreased quality of life. UV light exposure and smoking can exacerbate DLE, so sun protection and smoking cessation are both recommended in patients with DLE, although, admittedly, the latter is less relevant in the pediatric population.¹ Topical, intralesional, or systemic corticosteroids, with or without antimalarials, are the first line therapy for the management of DLE.¹ For refractory cases, some reports document the use of topical calcineurin inhibitors, dapsone, methotrexate, and topical or systemic retinoids.¹ For severe cases, intravenous immunoglobulin, ustekinumab, and rituximab also may be used.¹

References

1. Dermatol Ther. 2016 Apr 12 Epub.
2. Pediatr Dermatol. 2008 Mar-Apr;25(2):163-7.
3. Pediatr Dermatol. 2003 Mar-Apr;20(2):103-7.
4. J Am Acad Dermatol. 2015 Apr;72(4):628-33.
5. Pediatr Dermatol. 2016 Mar-Apr;33(2):200-8.
6. Pediatr Clin North Am. 2014 Apr;61(2):443-55.
7. Am J Dermatopathol. 2016 Feb;38(2):121-3.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg describe the diagnosis and treatment of discoid lupus erythematosus in children.

Discoid lupus erythematosus

Discoid lupus erythematosus (DLE) is a relatively common form of chronic cutaneous lupus, although its presentation in children is rare. The typical presentation of DLE is well-circumscribed, indurated, sometimes scaly round or oval plaques with pigmentary change, often red to purple in color. DLE also is clinically associated with telangiectasia, scarring, and follicular plugging, which has a characteristic appearance of “carpet tacking” beneath the scale.

When left untreated, these lesions may result in areas of long-term hypo- or hyperpigmentation, as well as atrophy and scarring.1 These cutaneous manifestations often are exacerbated by UV light exposure. This is particularly problematic because DLE most often affects the face, although lesions also can be found on the scalp, ears, trunk, extremities, and in the mouth as well.

Currently, there are few studies looking specifically at DLE in children and, based on the studies that have been done, there appear to be several important differences between the adult and pediatric populations. DLE affects women more than twice as much as men in the adult population, but reports vary as to whether this female predominance carries over to affected children.^2,3 Adults with DLE rarely have a family history of systemic lupus erythematosus (SLE), with rates reported between 1% and 4.4%. In children, however, the reported rates of family history increase tenfold to 11%-40%.²

One study showed that children with DLE progress to SLE at a rate of 23.5%-26%, which is higher than reported rates in adults of 5%-20%.^2,4 For this reason, repeated laboratory studies are essential in the follow-up of children diagnosed with DLE, given the possibility of a transition to systemic disease, particularly within the first year of diagnosis. Disseminated lesions can be a red flag for future progression to SLE.²

Differential diagnosis

The differential diagnosis of infiltrated annular lesions on the face and ears should include conditions such as tinea faciae, seborrheic dermatitis, granuloma annulare, cutaneous lymphoma, sarcoidosis, and leishmaniasis. When the lesions are present on the ear or nose, as in the case of this patient, relapsing polychonritis also may be considered.

Although histology plays a large part in diagnosing DLE, clinical presentation and recognizing the need for a biopsy are important.⁵ Tinea faciei, a fungal infection of the face, can present as erythematous scaly plaques.⁶ A thorough history and physical exam are important in differentiating tinea faciei from DLE because the former often begins as a small scaly papule that annularly expands outward to form larger plaque with scale around the outer rim, as opposed to DLE, which may have an adherent scale across the entire plaque.⁵ A potassium hydroxide (KOH) preparation of scraped scale from one of the lesions or a fungal culture can confirm the diagnosis of tinea faciei.⁶

Seborrheic dermatitis can be localized to the face and scalp and presents with greasy yellow scales. Early lesions of DLE can be difficult to differentiate from seborrheic dermatitis.

Infiltrated annular lesions on the face may represent granulomatous conditions such as granuloma annulare or sarcoidosis, but these lesions usually lack the presence of scale that can be seen in DLE.

Relapsing polychondritis presents as intermittent episodes of cartilage inflammation, usually affecting the cartilage of the ear, nose, and respiratory tract. Areas affected do not show changes on the surface of the skin as it occurs in DLE lesions.

As mentioned above, family history of SLE could indicate a potential for DLE in a small percentage of patients, but the clinical feature of the scaly plaques with the carpet tacking underneath the scale, caused by follicular plugging, is helpful in making the diagnosis clinically. Ultimately, the best way to differentiate anything resembling DLE is through histology and direct immunofluorescence (DIF). Histologic findings in DLE include epidermal atrophy, basal membrane cell vacuolization, hyperkeratosis, parakeratosis, corneal plugs, pseudoscysts, and acanthosis.³ The lupus band test is done using DIF and is a widely used tool for making the diagnosis of DLE based on the distribution of immunoglobulin deposition in the basement membrane zone.⁷

Treatment

Without timely diagnosis and treatment of DLE, the lesions can progress to scarring and atrophy, leading to a decreased quality of life. UV light exposure and smoking can exacerbate DLE, so sun protection and smoking cessation are both recommended in patients with DLE, although, admittedly, the latter is less relevant in the pediatric population.¹ Topical, intralesional, or systemic corticosteroids, with or without antimalarials, are the first line therapy for the management of DLE.¹ For refractory cases, some reports document the use of topical calcineurin inhibitors, dapsone, methotrexate, and topical or systemic retinoids.¹ For severe cases, intravenous immunoglobulin, ustekinumab, and rituximab also may be used.¹

References

1. Dermatol Ther. 2016 Apr 12 Epub.
2. Pediatr Dermatol. 2008 Mar-Apr;25(2):163-7.
3. Pediatr Dermatol. 2003 Mar-Apr;20(2):103-7.
4. J Am Acad Dermatol. 2015 Apr;72(4):628-33.
5. Pediatr Dermatol. 2016 Mar-Apr;33(2):200-8.
6. Pediatr Clin North Am. 2014 Apr;61(2):443-55.
7. Am J Dermatopathol. 2016 Feb;38(2):121-3.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

Presenters: Mary L Ehlenbach, MD, FAAP; Megan Z Cardoso, MD, FAAP; and Christina Kleier, ARNP, PNP

This session at PHM16 was focused on logistical tips on how to build a pediatric complex care program.  Presenters opened with a discussion of how to define children with medical complexity going through a variety of different methods including some research based aggregation of ICD-10 codes, referral from both families and other providers, and identifying patients by consumption of hospital resources. The presentation continued by highlighting that although medically complex children make up only a small percentage of the overall population of children, they account for about 1/3 of healthcare spending and due to advances in technology and medicine this group of children is growing in numbers. This group makes up about 10% of all pediatric admissions.

The session then went on to break down into four small groups which focused on details about how to create a complex care program and how to evaluate effectiveness of the program. Group 1 discussed methods of identifying patients that the program will serve. This included setting guidelines if a certain group or diagnosis should be excluded from the program. Different models of what services were also discussed which ranged from providing a comprehensive medical home to inpatient consults or care coordination services. The second group focused on what team members it may be beneficial to have involved. Team composition varied widely usually including MDs, NPs, social workers, RNs and at times a documentation expert who could aid with proper billing to boost revenue. The third group focused on how to measure quality services including family surveys of quantitative impact and satisfaction, PCP satisfaction. The final session consisted of the business and financial considerations of beginning a complex care program.

Key Takeaways:

1. Children with medical complexity are a growing population on which a large proportion of healthcare resources are utilized. A program dedicated to serving the needs of this population may be helpful in reducing costs and improving the patient and family experience during hospitalizations.
2. When working to initiate a complex care program:

   • Set clear guidelines about which children the program is intended to serve and in what capacity it will function.
   • Ensure the team composition is sustainable and meets the needs of the patients.
   • Aggregate data about if the program is helping. This may be difficult to quantify since these are mostly qualitative measures.
   • Include team members who are non-clinical to aid in improving hospital revenue and highlighting program benefits to the institution.

Presenters: Mary L Ehlenbach, MD, FAAP; Megan Z Cardoso, MD, FAAP; and Christina Kleier, ARNP, PNP

This session at PHM16 was focused on logistical tips on how to build a pediatric complex care program.  Presenters opened with a discussion of how to define children with medical complexity going through a variety of different methods including some research based aggregation of ICD-10 codes, referral from both families and other providers, and identifying patients by consumption of hospital resources. The presentation continued by highlighting that although medically complex children make up only a small percentage of the overall population of children, they account for about 1/3 of healthcare spending and due to advances in technology and medicine this group of children is growing in numbers. This group makes up about 10% of all pediatric admissions.

The session then went on to break down into four small groups which focused on details about how to create a complex care program and how to evaluate effectiveness of the program. Group 1 discussed methods of identifying patients that the program will serve. This included setting guidelines if a certain group or diagnosis should be excluded from the program. Different models of what services were also discussed which ranged from providing a comprehensive medical home to inpatient consults or care coordination services. The second group focused on what team members it may be beneficial to have involved. Team composition varied widely usually including MDs, NPs, social workers, RNs and at times a documentation expert who could aid with proper billing to boost revenue. The third group focused on how to measure quality services including family surveys of quantitative impact and satisfaction, PCP satisfaction. The final session consisted of the business and financial considerations of beginning a complex care program.

Key Takeaways:

1. Children with medical complexity are a growing population on which a large proportion of healthcare resources are utilized. A program dedicated to serving the needs of this population may be helpful in reducing costs and improving the patient and family experience during hospitalizations.
2. When working to initiate a complex care program:

   • Set clear guidelines about which children the program is intended to serve and in what capacity it will function.
   • Ensure the team composition is sustainable and meets the needs of the patients.
   • Aggregate data about if the program is helping. This may be difficult to quantify since these are mostly qualitative measures.
   • Include team members who are non-clinical to aid in improving hospital revenue and highlighting program benefits to the institution.

Presenters: Mary L Ehlenbach, MD, FAAP; Megan Z Cardoso, MD, FAAP; and Christina Kleier, ARNP, PNP

This session at PHM16 was focused on logistical tips on how to build a pediatric complex care program.  Presenters opened with a discussion of how to define children with medical complexity going through a variety of different methods including some research based aggregation of ICD-10 codes, referral from both families and other providers, and identifying patients by consumption of hospital resources. The presentation continued by highlighting that although medically complex children make up only a small percentage of the overall population of children, they account for about 1/3 of healthcare spending and due to advances in technology and medicine this group of children is growing in numbers. This group makes up about 10% of all pediatric admissions.

The session then went on to break down into four small groups which focused on details about how to create a complex care program and how to evaluate effectiveness of the program. Group 1 discussed methods of identifying patients that the program will serve. This included setting guidelines if a certain group or diagnosis should be excluded from the program. Different models of what services were also discussed which ranged from providing a comprehensive medical home to inpatient consults or care coordination services. The second group focused on what team members it may be beneficial to have involved. Team composition varied widely usually including MDs, NPs, social workers, RNs and at times a documentation expert who could aid with proper billing to boost revenue. The third group focused on how to measure quality services including family surveys of quantitative impact and satisfaction, PCP satisfaction. The final session consisted of the business and financial considerations of beginning a complex care program.

Key Takeaways:

1. Children with medical complexity are a growing population on which a large proportion of healthcare resources are utilized. A program dedicated to serving the needs of this population may be helpful in reducing costs and improving the patient and family experience during hospitalizations.
2. When working to initiate a complex care program:

   • Set clear guidelines about which children the program is intended to serve and in what capacity it will function.
   • Ensure the team composition is sustainable and meets the needs of the patients.
   • Aggregate data about if the program is helping. This may be difficult to quantify since these are mostly qualitative measures.
   • Include team members who are non-clinical to aid in improving hospital revenue and highlighting program benefits to the institution.

We recently reviewed the most current information on the epidemiology, clinical manifestations, and diagnosis of maternal and congenital Zika virus (ZV) infection.¹ We also offered tentative recommendations for reducing the risk of infection and for managing the treatment of women exposed to the virus.

In this update, we present new information on the broadened spectrum of anomalies now known to be causally related to congenital ZV infection and on the increasing number of serious neurologic complications directly related to ZV infection in adults. We also update recommendations for diagnosing maternal, fetal, and neonatal infection and present guidelines for preventing sexual transmission of ZV infection.

CASE Woman from Brazil gives birth to stillborn baby with microcephaly

A 23-year-old woman (G2P1) recently emigrated from Pernambuco in Brazil to the United States and now presents to the hospital in advanced labor. Based on results of first-trimester ultrasonography performed in Brazil, it is determined that she is at 39 weeks’ gestation. The patient has not had any prenatal care since early in the second trimester because of low income and lack of medical insurance. She reports no serious illness before or during the pregnancy.

In the labor and delivery suite, she rapidly delivers a stillborn female infant—5 pounds 3 ounces, growth restricted, with multiple congenital anomalies. Postmortem examination reveals microcephaly, ventriculomegaly, extensive brain atrophy, intracranial calcifications, cerebellar agenesis, cataracts, ocular calcifications, redundant scalp tissue, and multiple joint contractures.

What is the most likely cause of these multiple anomalies?

The patient’s findings are most consistent with a diagnosis of severe intrauterine infection. Possible pathogenic organisms include rubella virus, cytomegalovirus, lymphocytic choriomeningitis virus, toxoplasmosis, and ZV.² Given the patient’s recent move from Pernambuco in northeastern Brazil, the epicenter of the ZV epidemic in the Americas, the most likely diagnosis is congenital ZV infection.

The initial reports of congenital anomalies associated with ZV infection focused on microcephaly, usually defined as head circumference less than 3 standard deviations below the mean, or less than the third or fifth percentile for gestational age. Subsequent reports have linked many other serious central nervous system (CNS) anomalies to the virus. In a retrospective case series, de Fatima Vasco Aragao and colleagues³ described neuroimaging findings in 23 infants with presumed congenital ZV infection. Of the 22 with computed tomography scans, all had calcifications at the junction of cortical and subcortical white matter, 21 (95%) had disordered cortical development, 20 (91%) had a significant decrease in brain volume, 19 (86%) had ventriculomegaly, and half had distinct hypoplasia of either cerebellum or brainstem. In addition, of the 8 infants with magnetic resonance imaging (MRI) studies, 7 (88%) had an enlarged cisterna magna, 7 (88%) had delayed myelination, 6 (75%) had a simplified gyral pattern, and 3 (38%) had hypoplasia of corpus callosum.

De Paula Freitas and colleagues⁴ recently found congenital ZV infection associated with severe ocular abnormalities. Comprehensive ophthalmologic examination of 29 infants with microcephaly, presumed caused by congenital ZV infection, revealed 10 (35%) had abnormalities, which included focal pigment mottling, chorioretinal atrophy, hypoplasia and cupping of optic disk, loss of foveal reflex, macular atrophy, lens subluxation, and coloboma of iris.

Other conditions linked to congenital ZV infection include intrauterine growth restriction, redundant scalp tissue, contractures of multiple joints, and clubfoot.²

Bottom line. Although the ocular abnormalities are undetectable by prenatal ultrasound, many of the CNS and skeletal anomalies can be identified antenatally. Therefore, serial ultrasound examinations should be performed on adults who have a clinical illness consistent with ZV infection or who have traveled to an endemic area or have a sexual partner who has been in an endemic area. Patients should be assessed for possible microcephaly, ventriculomegaly, agenesis of corpus callosum, hypoplasia of cerebellum, and skeletal deformities.

Did ZV cause these anomalies?

How certain can we be that the anomalies present in the case patient’s baby were caused by ZV? In the past, and for many years, scientists relied on Koch’s 4 postulates (TABLE 1) to answer this question and establish a causal relationship between a microorganism and a specific clinical disease.⁵ Koch’s postulates have not been satisfied for the relationship between maternal ZV infection and congenital anomalies. Today’s more relevant standards for determining causality of a teratogen were published in 1994 by Shepard.⁶ In 2016, Rasmussen and colleagues⁷ found that the critical components of these criteria are fulfilled and concluded that there is little doubt ZV is a proven and extremely dangerous teratogen. See “Zika virus has been shown to be a direct cause of microcephaly”.

Rasmussen and colleagues⁷ also used Hill’s criteria to assess the evidence for causation. Hill’s systematic assessment is based on 9 factors (TABLE 2)⁸, and Rasmussen and colleagues⁷ concluded that the necessary 7 of these 9 criteria have been met (the experimental animal model criterion was not satisfied, and the biological gradient criterion was not applicable). Given their assessment of Shepard’s criteria,⁶ the authors argued that the link between maternal ZV infection and severe congenital anomalies has risen from association to well-defined causation.

How should ZV infection be confirmed in adults and newborns?

After our first review was published in March 2016,¹ the testing algorithm recommended by the US Centers for Disease Control and Prevention (CDC) was revised.⁹ Now, according to the CDC, if a patient has had symptoms of ZV infection for less than 5 days, serum and urine should be obtained for reverse transcriptase–polymerase chain reaction (RT-PCR) testing. If symptoms have been present for 5 to 14 days, urine should be tested by RT-PCR because urine samples appear to remain positive for virus longer than serum samples do. If RT-PCR is performed within the appropriate period and the result is negative, ZV infection is excluded; if the result is positive, acute ZV infection is confirmed, and additional testing is not indicated. RT-PCR can be performed by 2 commercial laboratories (Quest Diagnostics and LabCorp), state health departments, and the CDC.

If serum or urine is collected more than 5 days after symptom onset and the RT-PCR result is negative, the patient should have an immunoglobulin M (IgM) assay for ZV. If the assay result is negative, infection is excluded; if the result is positive or equivocal, additional testing is needed to ensure that the presence of the antibody does not reflect a cross-reaction to dengue or chikungunya virus. The confirmatory plaque reduction neutralization test (PRNT) is performed only by the CDC. To be considered positive, the PRNT result must be at least 4-fold higher than the dengue virus neutralizing antibody titer.

In patients with suspected Guillain-Barré syndrome (GBS), RT-PCR can be performed on cerebrospinal fluid. For suspected fetal or neonatal infection, RT-PCR can be performed on amniotic fluid, umbilical cord blood, and fetal and placental tissue.

CASE 2 Nonpregnant woman with possible Zika virus exposure presents to ED with neurologic symptoms

A 31-year-old nulligravid woman presents to the emergency department (ED) for evaluation of numbness, tingling, and weakness in the lower extremities and difficulty walking. She reports having had a low-grade fever and a fine disseminated macular rash 1 week earlier. She denies recent travel and exposure to friends or relatives with illness, but she says her husband travels extensively and was living and working in Puerto Rico. The patient has no other neurologic symptoms.

Serum and cerebrospinal fluid chemistries and MRI findings are normal. However, the ZV IgM assay is positive, and nerve conduction study results are consistent with GBS. The patient is admitted to the hospital, treated with intravenous immunoglobulin and given supportive care. Over 10 days, her neurologic condition gradually improves.

What is the link between ZV infection and serious neurologic complications in adults?

ZV infection has been associated with serious neurologic complications in adults. Investigators in several countries have reported dramatic increases in GBS cases during the ZV outbreak.¹⁰

GBS is an acute, immune-mediated, demyelinating peripheral neuropathy that can vary in presentation but most commonly manifests as a rapidly ascending paralysis. The disorder often is preceded by an immunization or live viral infection. In some patients, paralysis severely weakens the respiratory muscles and even the cranial nerves, and affected individuals may require intubation, ventilator support, and parenteral or enteral alimentation.

In a case-control study conducted duringthe 2013–2014 outbreak in French Polynesia, the association between ZV infection and GBS was evaluated in 3 groups of patients: 42 patients with GBS, 98 control patients, and 70 patients with ZV infection but no neurologic complications.¹¹ Symptoms of ZV infection were present in about 88% of the patients with GBS, and the median interval from viral infection to onset of neurologic symptoms was 6 days. The ZV IgM assay was positive in 93% of GBS cases. Nerve conduction study results were consistent with the acute motor axonal neuropathy of GBS. All patients were treated with intravenous immunoglobulin; 38% of patients had to be admitted to the intensive care unit, and 29% needed respiratory support. There were no fatalities. The overall incidence of GBS was 2.4 cases per 10,000 ZV infections.

Other neurologic complications that have been associated with ZV infection are meningoencephalitis,¹² brain ischemia,¹³ and myelitis.¹⁴

Bottom line. ZV infection may cause serious neurologic complications in adults. The most devastating complication is GBS, which can result in respiratory muscle paralysis and cranial nerve palsies.

How can patients prevent sexual transmission of ZV infection?

The ZV can be transmitted by sexual contact, including vaginal, anal, and oral sex.¹⁵ It is known to persist longer in semen than in blood or urine, though the exact duration remains unknown. Atkinson and colleagues¹⁶ reported RT-PCR detection of ZV RNA in semen about 62 days after onset of febrile illness—long after the virus became undetectable in blood.¹⁵

Mansuy and colleagues¹⁷ found that the viral load in semen was more than 100,000 times that in blood and urine more than 2 weeks after symptom onset.¹⁶ The ZV has been detected in saliva, urine, and breast milk. Although it has not been identified in vaginal secretions in humans, it has been detected in the vaginal secretions of nonhuman primates up to 7 days after subcutaneous inoculation of virus.¹⁸ In addition, the first case of female-to-male sexual transmission of ZV infection was just reported.¹⁹ In this report, transmission seems to have occurred on day 3 of the woman’s symptomatic illness, when she had unprotected vaginal intercourse with her partner. The partner became symptomatic 7 days after sexual exposure. To date, there is no evidence that infection is spread through kissing or breastfeeding.

The most recent recommendations from the CDC are that a man with symptomatic ZV infection wait at least 6 months before having unprotected sexual contact. In addition, a man who is asymptomatic after ZV exposure should wait at least 8 weeks before having unprotected sexual contact.¹⁷

A woman planning a pregnancy should know there is no evidence that prior ZV infection increases the risk of birth defects. However, a woman with a proven ZV infection should wait at least 8 weeks after symptom onset before trying to conceive. Even an asymptomatic woman with possible exposure should wait at least 8 weeks after the last exposure before attempting conception. In addition, given the risks associated with maternal and fetal infection, a man who has been exposed to the virus and who has a pregnant partner should abstain from unprotected sexual contact for the duration of the pregnancy.²⁰

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

We recently reviewed the most current information on the epidemiology, clinical manifestations, and diagnosis of maternal and congenital Zika virus (ZV) infection.¹ We also offered tentative recommendations for reducing the risk of infection and for managing the treatment of women exposed to the virus.

In this update, we present new information on the broadened spectrum of anomalies now known to be causally related to congenital ZV infection and on the increasing number of serious neurologic complications directly related to ZV infection in adults. We also update recommendations for diagnosing maternal, fetal, and neonatal infection and present guidelines for preventing sexual transmission of ZV infection.

CASE Woman from Brazil gives birth to stillborn baby with microcephaly

A 23-year-old woman (G2P1) recently emigrated from Pernambuco in Brazil to the United States and now presents to the hospital in advanced labor. Based on results of first-trimester ultrasonography performed in Brazil, it is determined that she is at 39 weeks’ gestation. The patient has not had any prenatal care since early in the second trimester because of low income and lack of medical insurance. She reports no serious illness before or during the pregnancy.

In the labor and delivery suite, she rapidly delivers a stillborn female infant—5 pounds 3 ounces, growth restricted, with multiple congenital anomalies. Postmortem examination reveals microcephaly, ventriculomegaly, extensive brain atrophy, intracranial calcifications, cerebellar agenesis, cataracts, ocular calcifications, redundant scalp tissue, and multiple joint contractures.

What is the most likely cause of these multiple anomalies?

The patient’s findings are most consistent with a diagnosis of severe intrauterine infection. Possible pathogenic organisms include rubella virus, cytomegalovirus, lymphocytic choriomeningitis virus, toxoplasmosis, and ZV.² Given the patient’s recent move from Pernambuco in northeastern Brazil, the epicenter of the ZV epidemic in the Americas, the most likely diagnosis is congenital ZV infection.

The initial reports of congenital anomalies associated with ZV infection focused on microcephaly, usually defined as head circumference less than 3 standard deviations below the mean, or less than the third or fifth percentile for gestational age. Subsequent reports have linked many other serious central nervous system (CNS) anomalies to the virus. In a retrospective case series, de Fatima Vasco Aragao and colleagues³ described neuroimaging findings in 23 infants with presumed congenital ZV infection. Of the 22 with computed tomography scans, all had calcifications at the junction of cortical and subcortical white matter, 21 (95%) had disordered cortical development, 20 (91%) had a significant decrease in brain volume, 19 (86%) had ventriculomegaly, and half had distinct hypoplasia of either cerebellum or brainstem. In addition, of the 8 infants with magnetic resonance imaging (MRI) studies, 7 (88%) had an enlarged cisterna magna, 7 (88%) had delayed myelination, 6 (75%) had a simplified gyral pattern, and 3 (38%) had hypoplasia of corpus callosum.

De Paula Freitas and colleagues⁴ recently found congenital ZV infection associated with severe ocular abnormalities. Comprehensive ophthalmologic examination of 29 infants with microcephaly, presumed caused by congenital ZV infection, revealed 10 (35%) had abnormalities, which included focal pigment mottling, chorioretinal atrophy, hypoplasia and cupping of optic disk, loss of foveal reflex, macular atrophy, lens subluxation, and coloboma of iris.

Other conditions linked to congenital ZV infection include intrauterine growth restriction, redundant scalp tissue, contractures of multiple joints, and clubfoot.²

Bottom line. Although the ocular abnormalities are undetectable by prenatal ultrasound, many of the CNS and skeletal anomalies can be identified antenatally. Therefore, serial ultrasound examinations should be performed on adults who have a clinical illness consistent with ZV infection or who have traveled to an endemic area or have a sexual partner who has been in an endemic area. Patients should be assessed for possible microcephaly, ventriculomegaly, agenesis of corpus callosum, hypoplasia of cerebellum, and skeletal deformities.

Did ZV cause these anomalies?

How certain can we be that the anomalies present in the case patient’s baby were caused by ZV? In the past, and for many years, scientists relied on Koch’s 4 postulates (TABLE 1) to answer this question and establish a causal relationship between a microorganism and a specific clinical disease.⁵ Koch’s postulates have not been satisfied for the relationship between maternal ZV infection and congenital anomalies. Today’s more relevant standards for determining causality of a teratogen were published in 1994 by Shepard.⁶ In 2016, Rasmussen and colleagues⁷ found that the critical components of these criteria are fulfilled and concluded that there is little doubt ZV is a proven and extremely dangerous teratogen. See “Zika virus has been shown to be a direct cause of microcephaly”.

Rasmussen and colleagues⁷ also used Hill’s criteria to assess the evidence for causation. Hill’s systematic assessment is based on 9 factors (TABLE 2)⁸, and Rasmussen and colleagues⁷ concluded that the necessary 7 of these 9 criteria have been met (the experimental animal model criterion was not satisfied, and the biological gradient criterion was not applicable). Given their assessment of Shepard’s criteria,⁶ the authors argued that the link between maternal ZV infection and severe congenital anomalies has risen from association to well-defined causation.

How should ZV infection be confirmed in adults and newborns?

After our first review was published in March 2016,¹ the testing algorithm recommended by the US Centers for Disease Control and Prevention (CDC) was revised.⁹ Now, according to the CDC, if a patient has had symptoms of ZV infection for less than 5 days, serum and urine should be obtained for reverse transcriptase–polymerase chain reaction (RT-PCR) testing. If symptoms have been present for 5 to 14 days, urine should be tested by RT-PCR because urine samples appear to remain positive for virus longer than serum samples do. If RT-PCR is performed within the appropriate period and the result is negative, ZV infection is excluded; if the result is positive, acute ZV infection is confirmed, and additional testing is not indicated. RT-PCR can be performed by 2 commercial laboratories (Quest Diagnostics and LabCorp), state health departments, and the CDC.

If serum or urine is collected more than 5 days after symptom onset and the RT-PCR result is negative, the patient should have an immunoglobulin M (IgM) assay for ZV. If the assay result is negative, infection is excluded; if the result is positive or equivocal, additional testing is needed to ensure that the presence of the antibody does not reflect a cross-reaction to dengue or chikungunya virus. The confirmatory plaque reduction neutralization test (PRNT) is performed only by the CDC. To be considered positive, the PRNT result must be at least 4-fold higher than the dengue virus neutralizing antibody titer.

In patients with suspected Guillain-Barré syndrome (GBS), RT-PCR can be performed on cerebrospinal fluid. For suspected fetal or neonatal infection, RT-PCR can be performed on amniotic fluid, umbilical cord blood, and fetal and placental tissue.

CASE 2 Nonpregnant woman with possible Zika virus exposure presents to ED with neurologic symptoms

A 31-year-old nulligravid woman presents to the emergency department (ED) for evaluation of numbness, tingling, and weakness in the lower extremities and difficulty walking. She reports having had a low-grade fever and a fine disseminated macular rash 1 week earlier. She denies recent travel and exposure to friends or relatives with illness, but she says her husband travels extensively and was living and working in Puerto Rico. The patient has no other neurologic symptoms.

Serum and cerebrospinal fluid chemistries and MRI findings are normal. However, the ZV IgM assay is positive, and nerve conduction study results are consistent with GBS. The patient is admitted to the hospital, treated with intravenous immunoglobulin and given supportive care. Over 10 days, her neurologic condition gradually improves.

What is the link between ZV infection and serious neurologic complications in adults?

ZV infection has been associated with serious neurologic complications in adults. Investigators in several countries have reported dramatic increases in GBS cases during the ZV outbreak.¹⁰

GBS is an acute, immune-mediated, demyelinating peripheral neuropathy that can vary in presentation but most commonly manifests as a rapidly ascending paralysis. The disorder often is preceded by an immunization or live viral infection. In some patients, paralysis severely weakens the respiratory muscles and even the cranial nerves, and affected individuals may require intubation, ventilator support, and parenteral or enteral alimentation.

In a case-control study conducted duringthe 2013–2014 outbreak in French Polynesia, the association between ZV infection and GBS was evaluated in 3 groups of patients: 42 patients with GBS, 98 control patients, and 70 patients with ZV infection but no neurologic complications.¹¹ Symptoms of ZV infection were present in about 88% of the patients with GBS, and the median interval from viral infection to onset of neurologic symptoms was 6 days. The ZV IgM assay was positive in 93% of GBS cases. Nerve conduction study results were consistent with the acute motor axonal neuropathy of GBS. All patients were treated with intravenous immunoglobulin; 38% of patients had to be admitted to the intensive care unit, and 29% needed respiratory support. There were no fatalities. The overall incidence of GBS was 2.4 cases per 10,000 ZV infections.

Other neurologic complications that have been associated with ZV infection are meningoencephalitis,¹² brain ischemia,¹³ and myelitis.¹⁴

Bottom line. ZV infection may cause serious neurologic complications in adults. The most devastating complication is GBS, which can result in respiratory muscle paralysis and cranial nerve palsies.

How can patients prevent sexual transmission of ZV infection?

The ZV can be transmitted by sexual contact, including vaginal, anal, and oral sex.¹⁵ It is known to persist longer in semen than in blood or urine, though the exact duration remains unknown. Atkinson and colleagues¹⁶ reported RT-PCR detection of ZV RNA in semen about 62 days after onset of febrile illness—long after the virus became undetectable in blood.¹⁵

Mansuy and colleagues¹⁷ found that the viral load in semen was more than 100,000 times that in blood and urine more than 2 weeks after symptom onset.¹⁶ The ZV has been detected in saliva, urine, and breast milk. Although it has not been identified in vaginal secretions in humans, it has been detected in the vaginal secretions of nonhuman primates up to 7 days after subcutaneous inoculation of virus.¹⁸ In addition, the first case of female-to-male sexual transmission of ZV infection was just reported.¹⁹ In this report, transmission seems to have occurred on day 3 of the woman’s symptomatic illness, when she had unprotected vaginal intercourse with her partner. The partner became symptomatic 7 days after sexual exposure. To date, there is no evidence that infection is spread through kissing or breastfeeding.

The most recent recommendations from the CDC are that a man with symptomatic ZV infection wait at least 6 months before having unprotected sexual contact. In addition, a man who is asymptomatic after ZV exposure should wait at least 8 weeks before having unprotected sexual contact.¹⁷

A woman planning a pregnancy should know there is no evidence that prior ZV infection increases the risk of birth defects. However, a woman with a proven ZV infection should wait at least 8 weeks after symptom onset before trying to conceive. Even an asymptomatic woman with possible exposure should wait at least 8 weeks after the last exposure before attempting conception. In addition, given the risks associated with maternal and fetal infection, a man who has been exposed to the virus and who has a pregnant partner should abstain from unprotected sexual contact for the duration of the pregnancy.²⁰

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

We recently reviewed the most current information on the epidemiology, clinical manifestations, and diagnosis of maternal and congenital Zika virus (ZV) infection.¹ We also offered tentative recommendations for reducing the risk of infection and for managing the treatment of women exposed to the virus.

In this update, we present new information on the broadened spectrum of anomalies now known to be causally related to congenital ZV infection and on the increasing number of serious neurologic complications directly related to ZV infection in adults. We also update recommendations for diagnosing maternal, fetal, and neonatal infection and present guidelines for preventing sexual transmission of ZV infection.

CASE Woman from Brazil gives birth to stillborn baby with microcephaly

A 23-year-old woman (G2P1) recently emigrated from Pernambuco in Brazil to the United States and now presents to the hospital in advanced labor. Based on results of first-trimester ultrasonography performed in Brazil, it is determined that she is at 39 weeks’ gestation. The patient has not had any prenatal care since early in the second trimester because of low income and lack of medical insurance. She reports no serious illness before or during the pregnancy.

In the labor and delivery suite, she rapidly delivers a stillborn female infant—5 pounds 3 ounces, growth restricted, with multiple congenital anomalies. Postmortem examination reveals microcephaly, ventriculomegaly, extensive brain atrophy, intracranial calcifications, cerebellar agenesis, cataracts, ocular calcifications, redundant scalp tissue, and multiple joint contractures.

What is the most likely cause of these multiple anomalies?

The patient’s findings are most consistent with a diagnosis of severe intrauterine infection. Possible pathogenic organisms include rubella virus, cytomegalovirus, lymphocytic choriomeningitis virus, toxoplasmosis, and ZV.² Given the patient’s recent move from Pernambuco in northeastern Brazil, the epicenter of the ZV epidemic in the Americas, the most likely diagnosis is congenital ZV infection.

The initial reports of congenital anomalies associated with ZV infection focused on microcephaly, usually defined as head circumference less than 3 standard deviations below the mean, or less than the third or fifth percentile for gestational age. Subsequent reports have linked many other serious central nervous system (CNS) anomalies to the virus. In a retrospective case series, de Fatima Vasco Aragao and colleagues³ described neuroimaging findings in 23 infants with presumed congenital ZV infection. Of the 22 with computed tomography scans, all had calcifications at the junction of cortical and subcortical white matter, 21 (95%) had disordered cortical development, 20 (91%) had a significant decrease in brain volume, 19 (86%) had ventriculomegaly, and half had distinct hypoplasia of either cerebellum or brainstem. In addition, of the 8 infants with magnetic resonance imaging (MRI) studies, 7 (88%) had an enlarged cisterna magna, 7 (88%) had delayed myelination, 6 (75%) had a simplified gyral pattern, and 3 (38%) had hypoplasia of corpus callosum.

De Paula Freitas and colleagues⁴ recently found congenital ZV infection associated with severe ocular abnormalities. Comprehensive ophthalmologic examination of 29 infants with microcephaly, presumed caused by congenital ZV infection, revealed 10 (35%) had abnormalities, which included focal pigment mottling, chorioretinal atrophy, hypoplasia and cupping of optic disk, loss of foveal reflex, macular atrophy, lens subluxation, and coloboma of iris.

Other conditions linked to congenital ZV infection include intrauterine growth restriction, redundant scalp tissue, contractures of multiple joints, and clubfoot.²

Bottom line. Although the ocular abnormalities are undetectable by prenatal ultrasound, many of the CNS and skeletal anomalies can be identified antenatally. Therefore, serial ultrasound examinations should be performed on adults who have a clinical illness consistent with ZV infection or who have traveled to an endemic area or have a sexual partner who has been in an endemic area. Patients should be assessed for possible microcephaly, ventriculomegaly, agenesis of corpus callosum, hypoplasia of cerebellum, and skeletal deformities.

Did ZV cause these anomalies?

How certain can we be that the anomalies present in the case patient’s baby were caused by ZV? In the past, and for many years, scientists relied on Koch’s 4 postulates (TABLE 1) to answer this question and establish a causal relationship between a microorganism and a specific clinical disease.⁵ Koch’s postulates have not been satisfied for the relationship between maternal ZV infection and congenital anomalies. Today’s more relevant standards for determining causality of a teratogen were published in 1994 by Shepard.⁶ In 2016, Rasmussen and colleagues⁷ found that the critical components of these criteria are fulfilled and concluded that there is little doubt ZV is a proven and extremely dangerous teratogen. See “Zika virus has been shown to be a direct cause of microcephaly”.

Rasmussen and colleagues⁷ also used Hill’s criteria to assess the evidence for causation. Hill’s systematic assessment is based on 9 factors (TABLE 2)⁸, and Rasmussen and colleagues⁷ concluded that the necessary 7 of these 9 criteria have been met (the experimental animal model criterion was not satisfied, and the biological gradient criterion was not applicable). Given their assessment of Shepard’s criteria,⁶ the authors argued that the link between maternal ZV infection and severe congenital anomalies has risen from association to well-defined causation.

How should ZV infection be confirmed in adults and newborns?

After our first review was published in March 2016,¹ the testing algorithm recommended by the US Centers for Disease Control and Prevention (CDC) was revised.⁹ Now, according to the CDC, if a patient has had symptoms of ZV infection for less than 5 days, serum and urine should be obtained for reverse transcriptase–polymerase chain reaction (RT-PCR) testing. If symptoms have been present for 5 to 14 days, urine should be tested by RT-PCR because urine samples appear to remain positive for virus longer than serum samples do. If RT-PCR is performed within the appropriate period and the result is negative, ZV infection is excluded; if the result is positive, acute ZV infection is confirmed, and additional testing is not indicated. RT-PCR can be performed by 2 commercial laboratories (Quest Diagnostics and LabCorp), state health departments, and the CDC.

If serum or urine is collected more than 5 days after symptom onset and the RT-PCR result is negative, the patient should have an immunoglobulin M (IgM) assay for ZV. If the assay result is negative, infection is excluded; if the result is positive or equivocal, additional testing is needed to ensure that the presence of the antibody does not reflect a cross-reaction to dengue or chikungunya virus. The confirmatory plaque reduction neutralization test (PRNT) is performed only by the CDC. To be considered positive, the PRNT result must be at least 4-fold higher than the dengue virus neutralizing antibody titer.

In patients with suspected Guillain-Barré syndrome (GBS), RT-PCR can be performed on cerebrospinal fluid. For suspected fetal or neonatal infection, RT-PCR can be performed on amniotic fluid, umbilical cord blood, and fetal and placental tissue.

CASE 2 Nonpregnant woman with possible Zika virus exposure presents to ED with neurologic symptoms

A 31-year-old nulligravid woman presents to the emergency department (ED) for evaluation of numbness, tingling, and weakness in the lower extremities and difficulty walking. She reports having had a low-grade fever and a fine disseminated macular rash 1 week earlier. She denies recent travel and exposure to friends or relatives with illness, but she says her husband travels extensively and was living and working in Puerto Rico. The patient has no other neurologic symptoms.

Serum and cerebrospinal fluid chemistries and MRI findings are normal. However, the ZV IgM assay is positive, and nerve conduction study results are consistent with GBS. The patient is admitted to the hospital, treated with intravenous immunoglobulin and given supportive care. Over 10 days, her neurologic condition gradually improves.

What is the link between ZV infection and serious neurologic complications in adults?

ZV infection has been associated with serious neurologic complications in adults. Investigators in several countries have reported dramatic increases in GBS cases during the ZV outbreak.¹⁰

GBS is an acute, immune-mediated, demyelinating peripheral neuropathy that can vary in presentation but most commonly manifests as a rapidly ascending paralysis. The disorder often is preceded by an immunization or live viral infection. In some patients, paralysis severely weakens the respiratory muscles and even the cranial nerves, and affected individuals may require intubation, ventilator support, and parenteral or enteral alimentation.

In a case-control study conducted duringthe 2013–2014 outbreak in French Polynesia, the association between ZV infection and GBS was evaluated in 3 groups of patients: 42 patients with GBS, 98 control patients, and 70 patients with ZV infection but no neurologic complications.¹¹ Symptoms of ZV infection were present in about 88% of the patients with GBS, and the median interval from viral infection to onset of neurologic symptoms was 6 days. The ZV IgM assay was positive in 93% of GBS cases. Nerve conduction study results were consistent with the acute motor axonal neuropathy of GBS. All patients were treated with intravenous immunoglobulin; 38% of patients had to be admitted to the intensive care unit, and 29% needed respiratory support. There were no fatalities. The overall incidence of GBS was 2.4 cases per 10,000 ZV infections.

Other neurologic complications that have been associated with ZV infection are meningoencephalitis,¹² brain ischemia,¹³ and myelitis.¹⁴

Bottom line. ZV infection may cause serious neurologic complications in adults. The most devastating complication is GBS, which can result in respiratory muscle paralysis and cranial nerve palsies.

How can patients prevent sexual transmission of ZV infection?

The ZV can be transmitted by sexual contact, including vaginal, anal, and oral sex.¹⁵ It is known to persist longer in semen than in blood or urine, though the exact duration remains unknown. Atkinson and colleagues¹⁶ reported RT-PCR detection of ZV RNA in semen about 62 days after onset of febrile illness—long after the virus became undetectable in blood.¹⁵

Mansuy and colleagues¹⁷ found that the viral load in semen was more than 100,000 times that in blood and urine more than 2 weeks after symptom onset.¹⁶ The ZV has been detected in saliva, urine, and breast milk. Although it has not been identified in vaginal secretions in humans, it has been detected in the vaginal secretions of nonhuman primates up to 7 days after subcutaneous inoculation of virus.¹⁸ In addition, the first case of female-to-male sexual transmission of ZV infection was just reported.¹⁹ In this report, transmission seems to have occurred on day 3 of the woman’s symptomatic illness, when she had unprotected vaginal intercourse with her partner. The partner became symptomatic 7 days after sexual exposure. To date, there is no evidence that infection is spread through kissing or breastfeeding.

The most recent recommendations from the CDC are that a man with symptomatic ZV infection wait at least 6 months before having unprotected sexual contact. In addition, a man who is asymptomatic after ZV exposure should wait at least 8 weeks before having unprotected sexual contact.¹⁷

A woman planning a pregnancy should know there is no evidence that prior ZV infection increases the risk of birth defects. However, a woman with a proven ZV infection should wait at least 8 weeks after symptom onset before trying to conceive. Even an asymptomatic woman with possible exposure should wait at least 8 weeks after the last exposure before attempting conception. In addition, given the risks associated with maternal and fetal infection, a man who has been exposed to the virus and who has a pregnant partner should abstain from unprotected sexual contact for the duration of the pregnancy.²⁰

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Contraception is an important tool that allows patients to carry out their reproductive-life plans. In the United States, the average woman desires 2 children.¹ To achieve this goal, she will spend more than 30 years of her reproductive life avoiding pregnancy.¹ The most effective reversible contraceptive methods, the intrauterine device (IUD) and the contraceptive implant, offer an efficient way to cover this significant period. Currently, American women more commonly choose an IUD than an implant by a factor 8 to 1.² Between 2002 and 2012, the percentage of US contraceptive users aged 15 to 44 using the IUD rose from 2% to 10%.²

Significant barriers to contraceptive access still exist, however. Although widespread reports have lauded the decrease in unintended pregnancies in the United States, improvement only has been marginal for women who live below the poverty level. In fact, for unintended pregnancy the gap between women above and below the poverty level has increased from a 2.6-fold difference in 1994 to a 5.6-fold difference in 2011 (FIGURE).³⁻⁵ Since the decrease in the unintended pregnancy rate is most likely related to an increase in contraceptive use, particularly the IUD, we are not providing equal contraceptive access to all women.⁵

Both the copper IUD and the 3 available levonorgestrel (LNG)-releasing intrauterine system (IUS) products provide safe and effective contraception. As IUD research expands, it is imperative for providers to stay up to date so patients can have full access to these devices.

In this article, we present important updates regarding IUD use that will help break down some continuing barriers to contraceptive access, including:

WHO study demonstrates LNG 52-mg IUS is highly effective for up to 7 years of use

Rowe P, Farley T, Peregoudov A, et al; IUD Research Group of the UNDP/UNFPA/WHO/World Bank Special Programme of Research; Development and Research Training in Human Reproduction. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93(6):498−506.

Currently, the 2 LNG 52-mg IUS products (Liletta, Mirena) approved by the US Food and Drug Administration (FDA) are available for use for 3 and 5 years, respectively. The pivotal approval trial for Liletta is still ongoing and is planned to continue for up to 7 years.⁶ The TCu380A (ParaGard) copper IUD is FDA approved for up to 10 years of use; however, this product initially was approved for only 4 years. The duration of use was expanded to 10 years based on continued clinical trials.

Based on current data, we will not need to wait for the Liletta pivotal trial to have clinical evidence of a longer duration of efficacy for the LNG 52-mg IUS. A collaborative group as part of the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction performed a multicenter, open-label randomized controlled trial to evaluate outcomes through 7 years of use of the LNG 52-mg IUS and the TCu380A IUD.

Details of the study

A total of 3,836 women were enrolled at 20 centers in Europe, Asia, South America, and China and were randomly assigned to one of the 2 products. Eligible women were aged 16 to 40 years, parous, and without known leiomyoma or recent pelvic infection. After excluding 15 failed IUD insertions, 1,910 women received an LNG 52-mg IUS and 1,911 received a TCu380A. Ultimately, 398 women in the LNG 52-mg IUS group and 682 in the TCu380A group completed 7-year follow-up with the IUD in place. Women were surveyed regarding pregnancy and method discontinuation.

Lower pregnancy rate, higher discontinuation with LNG IUS

The cumulative 7-year pregnancy rate among LNG 52-mg IUS users was significantly lower than among TCu380A users (0.53 per 100 women vs 2.45 per 100 women, respectively). All pregnancies in the LNG 52-mg IUS group occurred in the first 5 years of study follow-up--with no pregnancies in years 6 through 7 (TABLE). The cumulative pregnancy rate in the TCu380A group in this study is consistent with that in a previous long-term trial of this IUD.⁷

Early removal was significantly higher in the LNG 52-mg IUS group, with a cumulative discontinuation rate of 70.6 per 100 women, compared with 40.8 per 100 women in the TCu380A group. Significant cultural variation existed when it came to both rate and reason for discontinuation. Most women at Chinese centers cited amenorrhea and decreased bleeding as the primary reason for discontinuation, and they did so at twice the rate of women at non-Chinese centers.

The patterns of method discontinuation in this study were different from those found among US women. By comparison, a recent study in the United States had lower overall discontinuation rates and did not find decreased bleeding to be among the main reasons for LNG 52-mg IUS removal.⁷ In fact, most women who discontinued the LNG 52-mg IUS cited concerns about upcoming expiration as their reason for removal.

The results of this large study also generally corroborated the low-risk profile of IUDs. Only 1 reported IUD perforation occurred, for a rate of 0.03 per 1,000 women. Device expulsion rates were similar between the IUDs and were uncommon overall with 7-year rates of 8 to 9 per 100 women. Pelvic infection was cited as reason for removal in only 7 women (0.18 per 100 women) over 7 years.

What this evidence means for practiceThis exciting study is the first large-scale clinical trial demonstrating continued high efficacy with LNG 52-mg IUS use through 7 years. This information affords women extended contraceptive coverage. While additional research will be welcome, particularly in younger women who will maintain greater fertility across the IUS’s 7-year life span, we are confident in extending the 7-year duration for this IUS to our patients.

Additionally, the method discontinuation findings in this study highlight the importance of discussing the expected menstrual changes of hormonal IUS use with women prior to insertion so they can determine if the potential changes would be satisfactory. As the acceptability of medical menstrual suppression may be new to many women, providers should frame the adverse effects in this context. Providers can use this opportunity to review the noncontraceptive benefits of the hormonal IUS as well.

Novel combination of LNG 52-mg IUS and oral LNG 1.5 mg is promising for emergency contraception

Turok DK, Sanders JN, Thompson IS, Royer PA, Eggebroten J, Gawron LM. Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study. Contraception. 2016;93(6):526−532.

The copper IUD is superior for EC relative to oral agents and has the added benefit of providing ongoing highly effective contraception after placement.⁸ Despite this strong evidence, the copper IUD remains underutilized for this indication. Turok and colleagues noted that women in their clinic seeking IUDs for non-EC purposes preferred the LNG 52-mg IUS over the copper IUD. It is understandable that women might carry these preferences into EC encounters as well. Thus, the investigators devised a novel combination of LNG 52-mg IUS and oral LNG 1.5 mg, which provided both known EC benefit and same-day access to a more popular contraceptive device.

Details of the study

Women presenting for EC who desired same-day IUD placement were enrolled in the prospective cohort study. Eligible women had a negative urine pregnancy test, known last menstrual period (LMP), regular menstrual cycle, and reported unprotected intercourse within 120 hours prior to presentation. Importantly, women with multiple episodes of unprotected intercourse in the weeks prior to presentation were also included to provide a population more comparable to that encountered clinically. The women were then offered the choice of a TCu380A copper IUD or oral LNG EC with LNG 52-mg IUS placement. They were counseled on the potential increased risk of pregnancy with the novel oral LNG EC plus LNG IUS combination compared with the copper IUD. Participants were given a home pregnancy test that they were to complete in 2 weeks and then report the results to the clinic.

Of the 1,004 women presenting to the clinic for EC over the 16-month study period, 188 (18%) desired same-day IUD insertion. Of these, more opted for the oral LNG EC plus LNG IUS combination (n = 121, 64%) than the copper IUD (n = 67, 36%), demonstrating that women were often willing to accept a possible decrease in EC efficacy with the goal of obtaining their preferred lUD type.

Excluding failed insertion, undiagnosed uterine didelphys, and patient withdrawal, 110 women received the oral LNG EC plus LNG IUS and 66 received the copper IUD. Demographics were comparable between groups except for body mass index (BMI). Of note, more than half (61%) of the women who opted for the oral LNG EC plus LNG IUS combination were overweight or obese.

Both EC methods are effective, broadening options

All women who received the copper IUD followed up at 2 weeks, and no pregnancies were reported. Of the women who received oral LNG EC plus the LNG IUS, 107 (97%) had follow-up at 2 weeks. In this group, there was 1 reported ectopic pregnancy that ultimately required surgical management. However, further review of the patient's coital history suggested that conception occurred prior to IUD insertion, and the case was not classified by the investigators as an EC failure.

Although this study was not powered to detect pregnancy rate differences between the traditional copper IUD and the oral LNG EC plus LNG IUS combination, the results are promising. An important strength of this study is the presence of 2 high-risk groups for EC failure in the oral LNG EC plus LNG IUS group (elevated BMI and multiple episodes of unprotected intercourse).

What this evidence means for practiceEncounters for EC are important opportunities in which to discuss a woman’s reproductive goals. For women who are interested in an IUD, this study opens up the option of same-day placement of the LNG 52-mg IUS. While larger trials need to be conducted to obtain more information regarding pregnancy rates with an oral EC plus LNG IUS combination versus the TCu380A, offering such a combination is reasonable. Given that ulipristal acetate (UPA) is a more effective EC product, especially for women who are overweight or obese,⁹ offering a UPA EC plus LNG IUS combination may be a better alternative.

It is time to remove the STI screening barrier to same-day IUD insertion

Turok DK, Eisenberg DL, Teal SB, Keder LM, Creinin MD. A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement [published online ahead of print May 12, 2016]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2016.05017.

Provider concerns regarding the presence of pelvic infection remain a significant barrier to same-day IUD insertion. Older studies suggested a higher risk of pelvic infection in the first 20 days after IUD placement and extrapolated that pelvic infection was related to inserting an IUD in a woman at risk for STI.¹⁰ As a result, patients may be restricted from same-day IUD insertion by providers who think that obtaining results of STI testing is required prior to placement. Recently, a systematic review suggested, based on limited evidence, that IUD placement does not increase the risk of pelvic infection in asymptomatic women compared with those without an IUD.¹¹

Turok and colleagues (including M.D.C., coauthor of this article) reported results from a planned secondary analysis of A Comprehensive Contraceptive Efficacy and Safety Study of an IUS (ACCESS IUS), a component of the regulatory approval of the Liletta LNG 52-mg IUS. This analysis represents the first large-scale prospective investigation of pelvic infection rates during the first 2 years after IUD placement in US women.

Details of the study

Of the 1,751 women enrolled in the study, 1,714 had successful IUS insertions. Infection was assessed via baseline pelvic visual and bimanual examination and Chlamydia testing in all women. Gonorrhea testing was also performed in women who had not been tested with their current sexual partner. STI test results were not required for IUS insertion. Participants were assessed in person at 1, 3, 6, 12, and 24 months after insertion. Additional pelvic exams were performed as needed based on reported symptoms. At 6 months, 1 year, and 2 years, IUS continuation was reported in 1,553 (90.6%), 1,401 (81.7%), and 1,157 (67.3%) women, respectively.

Nearly all women received baseline STI testing (98.4%); however, results were not available prior to same-day IUS insertion for 79.6% of participants. Twenty-nine (1.7%) women had positive baseline STI tests (25 for Chlamydia, 3 for gonorrhea, 1 for both). Of these, only 6 women had results available prior to IUS placement. All women with a positive STI test were treated, and the IUS was left in place. Importantly, none of these women developed pelvic infection in the subsequent 2 years of follow-up and none requested IUS removal.

Infection risk is low with IUD placement

Among women with negative baseline STI tests, there were only 9 (0.5%) clinical diagnoses of pelvic infections over the first 2 years of follow-up. Diagnosis was typically made based on physical examination findings. Most women underwent repeat Chlamydia and gonorrhea testing at the time of pelvic infection diagnosis, and none had positive results. There were no medically recommended IUS removals; 2 women with pelvic infection requested IUS removal per their preference.

Three of the 9 women with pelvic infections were diagnosed within 1 week of IUS placement, 1 at 39 days after placement, and the remaining 5 more than 6 months after placement, suggesting that pelvic infection is not temporally related to IUS placement. Most women were successfully treated as outpatients.

What this evidence means for practiceThis study provides further reassurance regarding the low risk of pelvic infection among women with an LNG IUS. Insertion of an IUS should not be delayed to await results of Chlamydia or gonorrhea testing in a woman without clinical evidence of pelvic infection. Risk-based, as opposed to universal testing, is imperative.¹² These recommendations are in agreement with current recommendations of the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists.^13,14 Practices that employ 2-visit protocols unnecessarily limit women’s access to the IUS, as research has shown that nearly half of women desiring an IUD do not return for device placement if a second encounter is required.¹⁵

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Contraception is an important tool that allows patients to carry out their reproductive-life plans. In the United States, the average woman desires 2 children.¹ To achieve this goal, she will spend more than 30 years of her reproductive life avoiding pregnancy.¹ The most effective reversible contraceptive methods, the intrauterine device (IUD) and the contraceptive implant, offer an efficient way to cover this significant period. Currently, American women more commonly choose an IUD than an implant by a factor 8 to 1.² Between 2002 and 2012, the percentage of US contraceptive users aged 15 to 44 using the IUD rose from 2% to 10%.²

Significant barriers to contraceptive access still exist, however. Although widespread reports have lauded the decrease in unintended pregnancies in the United States, improvement only has been marginal for women who live below the poverty level. In fact, for unintended pregnancy the gap between women above and below the poverty level has increased from a 2.6-fold difference in 1994 to a 5.6-fold difference in 2011 (FIGURE).³⁻⁵ Since the decrease in the unintended pregnancy rate is most likely related to an increase in contraceptive use, particularly the IUD, we are not providing equal contraceptive access to all women.⁵

Both the copper IUD and the 3 available levonorgestrel (LNG)-releasing intrauterine system (IUS) products provide safe and effective contraception. As IUD research expands, it is imperative for providers to stay up to date so patients can have full access to these devices.

In this article, we present important updates regarding IUD use that will help break down some continuing barriers to contraceptive access, including:

WHO study demonstrates LNG 52-mg IUS is highly effective for up to 7 years of use

Rowe P, Farley T, Peregoudov A, et al; IUD Research Group of the UNDP/UNFPA/WHO/World Bank Special Programme of Research; Development and Research Training in Human Reproduction. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93(6):498−506.

Currently, the 2 LNG 52-mg IUS products (Liletta, Mirena) approved by the US Food and Drug Administration (FDA) are available for use for 3 and 5 years, respectively. The pivotal approval trial for Liletta is still ongoing and is planned to continue for up to 7 years.⁶ The TCu380A (ParaGard) copper IUD is FDA approved for up to 10 years of use; however, this product initially was approved for only 4 years. The duration of use was expanded to 10 years based on continued clinical trials.

Based on current data, we will not need to wait for the Liletta pivotal trial to have clinical evidence of a longer duration of efficacy for the LNG 52-mg IUS. A collaborative group as part of the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction performed a multicenter, open-label randomized controlled trial to evaluate outcomes through 7 years of use of the LNG 52-mg IUS and the TCu380A IUD.

Details of the study

A total of 3,836 women were enrolled at 20 centers in Europe, Asia, South America, and China and were randomly assigned to one of the 2 products. Eligible women were aged 16 to 40 years, parous, and without known leiomyoma or recent pelvic infection. After excluding 15 failed IUD insertions, 1,910 women received an LNG 52-mg IUS and 1,911 received a TCu380A. Ultimately, 398 women in the LNG 52-mg IUS group and 682 in the TCu380A group completed 7-year follow-up with the IUD in place. Women were surveyed regarding pregnancy and method discontinuation.

Lower pregnancy rate, higher discontinuation with LNG IUS

The cumulative 7-year pregnancy rate among LNG 52-mg IUS users was significantly lower than among TCu380A users (0.53 per 100 women vs 2.45 per 100 women, respectively). All pregnancies in the LNG 52-mg IUS group occurred in the first 5 years of study follow-up--with no pregnancies in years 6 through 7 (TABLE). The cumulative pregnancy rate in the TCu380A group in this study is consistent with that in a previous long-term trial of this IUD.⁷

Early removal was significantly higher in the LNG 52-mg IUS group, with a cumulative discontinuation rate of 70.6 per 100 women, compared with 40.8 per 100 women in the TCu380A group. Significant cultural variation existed when it came to both rate and reason for discontinuation. Most women at Chinese centers cited amenorrhea and decreased bleeding as the primary reason for discontinuation, and they did so at twice the rate of women at non-Chinese centers.

The patterns of method discontinuation in this study were different from those found among US women. By comparison, a recent study in the United States had lower overall discontinuation rates and did not find decreased bleeding to be among the main reasons for LNG 52-mg IUS removal.⁷ In fact, most women who discontinued the LNG 52-mg IUS cited concerns about upcoming expiration as their reason for removal.

The results of this large study also generally corroborated the low-risk profile of IUDs. Only 1 reported IUD perforation occurred, for a rate of 0.03 per 1,000 women. Device expulsion rates were similar between the IUDs and were uncommon overall with 7-year rates of 8 to 9 per 100 women. Pelvic infection was cited as reason for removal in only 7 women (0.18 per 100 women) over 7 years.

What this evidence means for practiceThis exciting study is the first large-scale clinical trial demonstrating continued high efficacy with LNG 52-mg IUS use through 7 years. This information affords women extended contraceptive coverage. While additional research will be welcome, particularly in younger women who will maintain greater fertility across the IUS’s 7-year life span, we are confident in extending the 7-year duration for this IUS to our patients.

Additionally, the method discontinuation findings in this study highlight the importance of discussing the expected menstrual changes of hormonal IUS use with women prior to insertion so they can determine if the potential changes would be satisfactory. As the acceptability of medical menstrual suppression may be new to many women, providers should frame the adverse effects in this context. Providers can use this opportunity to review the noncontraceptive benefits of the hormonal IUS as well.

Novel combination of LNG 52-mg IUS and oral LNG 1.5 mg is promising for emergency contraception

Turok DK, Sanders JN, Thompson IS, Royer PA, Eggebroten J, Gawron LM. Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study. Contraception. 2016;93(6):526−532.

The copper IUD is superior for EC relative to oral agents and has the added benefit of providing ongoing highly effective contraception after placement.⁸ Despite this strong evidence, the copper IUD remains underutilized for this indication. Turok and colleagues noted that women in their clinic seeking IUDs for non-EC purposes preferred the LNG 52-mg IUS over the copper IUD. It is understandable that women might carry these preferences into EC encounters as well. Thus, the investigators devised a novel combination of LNG 52-mg IUS and oral LNG 1.5 mg, which provided both known EC benefit and same-day access to a more popular contraceptive device.

Details of the study

Women presenting for EC who desired same-day IUD placement were enrolled in the prospective cohort study. Eligible women had a negative urine pregnancy test, known last menstrual period (LMP), regular menstrual cycle, and reported unprotected intercourse within 120 hours prior to presentation. Importantly, women with multiple episodes of unprotected intercourse in the weeks prior to presentation were also included to provide a population more comparable to that encountered clinically. The women were then offered the choice of a TCu380A copper IUD or oral LNG EC with LNG 52-mg IUS placement. They were counseled on the potential increased risk of pregnancy with the novel oral LNG EC plus LNG IUS combination compared with the copper IUD. Participants were given a home pregnancy test that they were to complete in 2 weeks and then report the results to the clinic.

Of the 1,004 women presenting to the clinic for EC over the 16-month study period, 188 (18%) desired same-day IUD insertion. Of these, more opted for the oral LNG EC plus LNG IUS combination (n = 121, 64%) than the copper IUD (n = 67, 36%), demonstrating that women were often willing to accept a possible decrease in EC efficacy with the goal of obtaining their preferred lUD type.

Excluding failed insertion, undiagnosed uterine didelphys, and patient withdrawal, 110 women received the oral LNG EC plus LNG IUS and 66 received the copper IUD. Demographics were comparable between groups except for body mass index (BMI). Of note, more than half (61%) of the women who opted for the oral LNG EC plus LNG IUS combination were overweight or obese.

Both EC methods are effective, broadening options

All women who received the copper IUD followed up at 2 weeks, and no pregnancies were reported. Of the women who received oral LNG EC plus the LNG IUS, 107 (97%) had follow-up at 2 weeks. In this group, there was 1 reported ectopic pregnancy that ultimately required surgical management. However, further review of the patient's coital history suggested that conception occurred prior to IUD insertion, and the case was not classified by the investigators as an EC failure.

Although this study was not powered to detect pregnancy rate differences between the traditional copper IUD and the oral LNG EC plus LNG IUS combination, the results are promising. An important strength of this study is the presence of 2 high-risk groups for EC failure in the oral LNG EC plus LNG IUS group (elevated BMI and multiple episodes of unprotected intercourse).

What this evidence means for practiceEncounters for EC are important opportunities in which to discuss a woman’s reproductive goals. For women who are interested in an IUD, this study opens up the option of same-day placement of the LNG 52-mg IUS. While larger trials need to be conducted to obtain more information regarding pregnancy rates with an oral EC plus LNG IUS combination versus the TCu380A, offering such a combination is reasonable. Given that ulipristal acetate (UPA) is a more effective EC product, especially for women who are overweight or obese,⁹ offering a UPA EC plus LNG IUS combination may be a better alternative.

It is time to remove the STI screening barrier to same-day IUD insertion

Turok DK, Eisenberg DL, Teal SB, Keder LM, Creinin MD. A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement [published online ahead of print May 12, 2016]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2016.05017.

Provider concerns regarding the presence of pelvic infection remain a significant barrier to same-day IUD insertion. Older studies suggested a higher risk of pelvic infection in the first 20 days after IUD placement and extrapolated that pelvic infection was related to inserting an IUD in a woman at risk for STI.¹⁰ As a result, patients may be restricted from same-day IUD insertion by providers who think that obtaining results of STI testing is required prior to placement. Recently, a systematic review suggested, based on limited evidence, that IUD placement does not increase the risk of pelvic infection in asymptomatic women compared with those without an IUD.¹¹

Turok and colleagues (including M.D.C., coauthor of this article) reported results from a planned secondary analysis of A Comprehensive Contraceptive Efficacy and Safety Study of an IUS (ACCESS IUS), a component of the regulatory approval of the Liletta LNG 52-mg IUS. This analysis represents the first large-scale prospective investigation of pelvic infection rates during the first 2 years after IUD placement in US women.

Details of the study

Of the 1,751 women enrolled in the study, 1,714 had successful IUS insertions. Infection was assessed via baseline pelvic visual and bimanual examination and Chlamydia testing in all women. Gonorrhea testing was also performed in women who had not been tested with their current sexual partner. STI test results were not required for IUS insertion. Participants were assessed in person at 1, 3, 6, 12, and 24 months after insertion. Additional pelvic exams were performed as needed based on reported symptoms. At 6 months, 1 year, and 2 years, IUS continuation was reported in 1,553 (90.6%), 1,401 (81.7%), and 1,157 (67.3%) women, respectively.

Nearly all women received baseline STI testing (98.4%); however, results were not available prior to same-day IUS insertion for 79.6% of participants. Twenty-nine (1.7%) women had positive baseline STI tests (25 for Chlamydia, 3 for gonorrhea, 1 for both). Of these, only 6 women had results available prior to IUS placement. All women with a positive STI test were treated, and the IUS was left in place. Importantly, none of these women developed pelvic infection in the subsequent 2 years of follow-up and none requested IUS removal.

Infection risk is low with IUD placement

Among women with negative baseline STI tests, there were only 9 (0.5%) clinical diagnoses of pelvic infections over the first 2 years of follow-up. Diagnosis was typically made based on physical examination findings. Most women underwent repeat Chlamydia and gonorrhea testing at the time of pelvic infection diagnosis, and none had positive results. There were no medically recommended IUS removals; 2 women with pelvic infection requested IUS removal per their preference.

Three of the 9 women with pelvic infections were diagnosed within 1 week of IUS placement, 1 at 39 days after placement, and the remaining 5 more than 6 months after placement, suggesting that pelvic infection is not temporally related to IUS placement. Most women were successfully treated as outpatients.

What this evidence means for practiceThis study provides further reassurance regarding the low risk of pelvic infection among women with an LNG IUS. Insertion of an IUS should not be delayed to await results of Chlamydia or gonorrhea testing in a woman without clinical evidence of pelvic infection. Risk-based, as opposed to universal testing, is imperative.¹² These recommendations are in agreement with current recommendations of the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists.^13,14 Practices that employ 2-visit protocols unnecessarily limit women’s access to the IUS, as research has shown that nearly half of women desiring an IUD do not return for device placement if a second encounter is required.¹⁵

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Contraception is an important tool that allows patients to carry out their reproductive-life plans. In the United States, the average woman desires 2 children.¹ To achieve this goal, she will spend more than 30 years of her reproductive life avoiding pregnancy.¹ The most effective reversible contraceptive methods, the intrauterine device (IUD) and the contraceptive implant, offer an efficient way to cover this significant period. Currently, American women more commonly choose an IUD than an implant by a factor 8 to 1.² Between 2002 and 2012, the percentage of US contraceptive users aged 15 to 44 using the IUD rose from 2% to 10%.²

Significant barriers to contraceptive access still exist, however. Although widespread reports have lauded the decrease in unintended pregnancies in the United States, improvement only has been marginal for women who live below the poverty level. In fact, for unintended pregnancy the gap between women above and below the poverty level has increased from a 2.6-fold difference in 1994 to a 5.6-fold difference in 2011 (FIGURE).³⁻⁵ Since the decrease in the unintended pregnancy rate is most likely related to an increase in contraceptive use, particularly the IUD, we are not providing equal contraceptive access to all women.⁵

Both the copper IUD and the 3 available levonorgestrel (LNG)-releasing intrauterine system (IUS) products provide safe and effective contraception. As IUD research expands, it is imperative for providers to stay up to date so patients can have full access to these devices.

In this article, we present important updates regarding IUD use that will help break down some continuing barriers to contraceptive access, including:

WHO study demonstrates LNG 52-mg IUS is highly effective for up to 7 years of use

Rowe P, Farley T, Peregoudov A, et al; IUD Research Group of the UNDP/UNFPA/WHO/World Bank Special Programme of Research; Development and Research Training in Human Reproduction. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception. 2016;93(6):498−506.

Currently, the 2 LNG 52-mg IUS products (Liletta, Mirena) approved by the US Food and Drug Administration (FDA) are available for use for 3 and 5 years, respectively. The pivotal approval trial for Liletta is still ongoing and is planned to continue for up to 7 years.⁶ The TCu380A (ParaGard) copper IUD is FDA approved for up to 10 years of use; however, this product initially was approved for only 4 years. The duration of use was expanded to 10 years based on continued clinical trials.

Based on current data, we will not need to wait for the Liletta pivotal trial to have clinical evidence of a longer duration of efficacy for the LNG 52-mg IUS. A collaborative group as part of the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction performed a multicenter, open-label randomized controlled trial to evaluate outcomes through 7 years of use of the LNG 52-mg IUS and the TCu380A IUD.

Details of the study

A total of 3,836 women were enrolled at 20 centers in Europe, Asia, South America, and China and were randomly assigned to one of the 2 products. Eligible women were aged 16 to 40 years, parous, and without known leiomyoma or recent pelvic infection. After excluding 15 failed IUD insertions, 1,910 women received an LNG 52-mg IUS and 1,911 received a TCu380A. Ultimately, 398 women in the LNG 52-mg IUS group and 682 in the TCu380A group completed 7-year follow-up with the IUD in place. Women were surveyed regarding pregnancy and method discontinuation.

Lower pregnancy rate, higher discontinuation with LNG IUS

The cumulative 7-year pregnancy rate among LNG 52-mg IUS users was significantly lower than among TCu380A users (0.53 per 100 women vs 2.45 per 100 women, respectively). All pregnancies in the LNG 52-mg IUS group occurred in the first 5 years of study follow-up--with no pregnancies in years 6 through 7 (TABLE). The cumulative pregnancy rate in the TCu380A group in this study is consistent with that in a previous long-term trial of this IUD.⁷

Early removal was significantly higher in the LNG 52-mg IUS group, with a cumulative discontinuation rate of 70.6 per 100 women, compared with 40.8 per 100 women in the TCu380A group. Significant cultural variation existed when it came to both rate and reason for discontinuation. Most women at Chinese centers cited amenorrhea and decreased bleeding as the primary reason for discontinuation, and they did so at twice the rate of women at non-Chinese centers.

The patterns of method discontinuation in this study were different from those found among US women. By comparison, a recent study in the United States had lower overall discontinuation rates and did not find decreased bleeding to be among the main reasons for LNG 52-mg IUS removal.⁷ In fact, most women who discontinued the LNG 52-mg IUS cited concerns about upcoming expiration as their reason for removal.

The results of this large study also generally corroborated the low-risk profile of IUDs. Only 1 reported IUD perforation occurred, for a rate of 0.03 per 1,000 women. Device expulsion rates were similar between the IUDs and were uncommon overall with 7-year rates of 8 to 9 per 100 women. Pelvic infection was cited as reason for removal in only 7 women (0.18 per 100 women) over 7 years.

What this evidence means for practiceThis exciting study is the first large-scale clinical trial demonstrating continued high efficacy with LNG 52-mg IUS use through 7 years. This information affords women extended contraceptive coverage. While additional research will be welcome, particularly in younger women who will maintain greater fertility across the IUS’s 7-year life span, we are confident in extending the 7-year duration for this IUS to our patients.

Additionally, the method discontinuation findings in this study highlight the importance of discussing the expected menstrual changes of hormonal IUS use with women prior to insertion so they can determine if the potential changes would be satisfactory. As the acceptability of medical menstrual suppression may be new to many women, providers should frame the adverse effects in this context. Providers can use this opportunity to review the noncontraceptive benefits of the hormonal IUS as well.

Novel combination of LNG 52-mg IUS and oral LNG 1.5 mg is promising for emergency contraception

Turok DK, Sanders JN, Thompson IS, Royer PA, Eggebroten J, Gawron LM. Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study. Contraception. 2016;93(6):526−532.

The copper IUD is superior for EC relative to oral agents and has the added benefit of providing ongoing highly effective contraception after placement.⁸ Despite this strong evidence, the copper IUD remains underutilized for this indication. Turok and colleagues noted that women in their clinic seeking IUDs for non-EC purposes preferred the LNG 52-mg IUS over the copper IUD. It is understandable that women might carry these preferences into EC encounters as well. Thus, the investigators devised a novel combination of LNG 52-mg IUS and oral LNG 1.5 mg, which provided both known EC benefit and same-day access to a more popular contraceptive device.

Details of the study

Women presenting for EC who desired same-day IUD placement were enrolled in the prospective cohort study. Eligible women had a negative urine pregnancy test, known last menstrual period (LMP), regular menstrual cycle, and reported unprotected intercourse within 120 hours prior to presentation. Importantly, women with multiple episodes of unprotected intercourse in the weeks prior to presentation were also included to provide a population more comparable to that encountered clinically. The women were then offered the choice of a TCu380A copper IUD or oral LNG EC with LNG 52-mg IUS placement. They were counseled on the potential increased risk of pregnancy with the novel oral LNG EC plus LNG IUS combination compared with the copper IUD. Participants were given a home pregnancy test that they were to complete in 2 weeks and then report the results to the clinic.

Of the 1,004 women presenting to the clinic for EC over the 16-month study period, 188 (18%) desired same-day IUD insertion. Of these, more opted for the oral LNG EC plus LNG IUS combination (n = 121, 64%) than the copper IUD (n = 67, 36%), demonstrating that women were often willing to accept a possible decrease in EC efficacy with the goal of obtaining their preferred lUD type.

Excluding failed insertion, undiagnosed uterine didelphys, and patient withdrawal, 110 women received the oral LNG EC plus LNG IUS and 66 received the copper IUD. Demographics were comparable between groups except for body mass index (BMI). Of note, more than half (61%) of the women who opted for the oral LNG EC plus LNG IUS combination were overweight or obese.

Both EC methods are effective, broadening options

All women who received the copper IUD followed up at 2 weeks, and no pregnancies were reported. Of the women who received oral LNG EC plus the LNG IUS, 107 (97%) had follow-up at 2 weeks. In this group, there was 1 reported ectopic pregnancy that ultimately required surgical management. However, further review of the patient's coital history suggested that conception occurred prior to IUD insertion, and the case was not classified by the investigators as an EC failure.

Although this study was not powered to detect pregnancy rate differences between the traditional copper IUD and the oral LNG EC plus LNG IUS combination, the results are promising. An important strength of this study is the presence of 2 high-risk groups for EC failure in the oral LNG EC plus LNG IUS group (elevated BMI and multiple episodes of unprotected intercourse).

What this evidence means for practiceEncounters for EC are important opportunities in which to discuss a woman’s reproductive goals. For women who are interested in an IUD, this study opens up the option of same-day placement of the LNG 52-mg IUS. While larger trials need to be conducted to obtain more information regarding pregnancy rates with an oral EC plus LNG IUS combination versus the TCu380A, offering such a combination is reasonable. Given that ulipristal acetate (UPA) is a more effective EC product, especially for women who are overweight or obese,⁹ offering a UPA EC plus LNG IUS combination may be a better alternative.

It is time to remove the STI screening barrier to same-day IUD insertion

Turok DK, Eisenberg DL, Teal SB, Keder LM, Creinin MD. A prospective assessment of pelvic infection risk following same-day sexually transmitted infection testing and levonorgestrel intrauterine system placement [published online ahead of print May 12, 2016]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2016.05017.

Provider concerns regarding the presence of pelvic infection remain a significant barrier to same-day IUD insertion. Older studies suggested a higher risk of pelvic infection in the first 20 days after IUD placement and extrapolated that pelvic infection was related to inserting an IUD in a woman at risk for STI.¹⁰ As a result, patients may be restricted from same-day IUD insertion by providers who think that obtaining results of STI testing is required prior to placement. Recently, a systematic review suggested, based on limited evidence, that IUD placement does not increase the risk of pelvic infection in asymptomatic women compared with those without an IUD.¹¹

Turok and colleagues (including M.D.C., coauthor of this article) reported results from a planned secondary analysis of A Comprehensive Contraceptive Efficacy and Safety Study of an IUS (ACCESS IUS), a component of the regulatory approval of the Liletta LNG 52-mg IUS. This analysis represents the first large-scale prospective investigation of pelvic infection rates during the first 2 years after IUD placement in US women.

Details of the study

Of the 1,751 women enrolled in the study, 1,714 had successful IUS insertions. Infection was assessed via baseline pelvic visual and bimanual examination and Chlamydia testing in all women. Gonorrhea testing was also performed in women who had not been tested with their current sexual partner. STI test results were not required for IUS insertion. Participants were assessed in person at 1, 3, 6, 12, and 24 months after insertion. Additional pelvic exams were performed as needed based on reported symptoms. At 6 months, 1 year, and 2 years, IUS continuation was reported in 1,553 (90.6%), 1,401 (81.7%), and 1,157 (67.3%) women, respectively.

Nearly all women received baseline STI testing (98.4%); however, results were not available prior to same-day IUS insertion for 79.6% of participants. Twenty-nine (1.7%) women had positive baseline STI tests (25 for Chlamydia, 3 for gonorrhea, 1 for both). Of these, only 6 women had results available prior to IUS placement. All women with a positive STI test were treated, and the IUS was left in place. Importantly, none of these women developed pelvic infection in the subsequent 2 years of follow-up and none requested IUS removal.

Infection risk is low with IUD placement

Among women with negative baseline STI tests, there were only 9 (0.5%) clinical diagnoses of pelvic infections over the first 2 years of follow-up. Diagnosis was typically made based on physical examination findings. Most women underwent repeat Chlamydia and gonorrhea testing at the time of pelvic infection diagnosis, and none had positive results. There were no medically recommended IUS removals; 2 women with pelvic infection requested IUS removal per their preference.

Three of the 9 women with pelvic infections were diagnosed within 1 week of IUS placement, 1 at 39 days after placement, and the remaining 5 more than 6 months after placement, suggesting that pelvic infection is not temporally related to IUS placement. Most women were successfully treated as outpatients.

What this evidence means for practiceThis study provides further reassurance regarding the low risk of pelvic infection among women with an LNG IUS. Insertion of an IUS should not be delayed to await results of Chlamydia or gonorrhea testing in a woman without clinical evidence of pelvic infection. Risk-based, as opposed to universal testing, is imperative.¹² These recommendations are in agreement with current recommendations of the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists.^13,14 Practices that employ 2-visit protocols unnecessarily limit women’s access to the IUS, as research has shown that nearly half of women desiring an IUD do not return for device placement if a second encounter is required.¹⁵

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Rates of cesarean delivery in the second stage of labor have increased dramatically over the past few years.¹ Compared with cesarean delivery prior to labor, second-stage labor cesarean is associated with a higher risk to both the mother and the fetus; risks include excessive bleeding, lower uterine segment extensions, injuries to the maternal ureters or bladder, and injury to the fetus.²⁻⁴ The risk is increased even further if the fetal head is deeply impacted in the pelvis. What can we do to avoid and manage such situations?

Anticipate an impacted fetal headThe true incidence of an impacted fetal head at the time of cesarean is not known, although a number of risk factors have been described (TABLE). Obstetric care providers should be aware of these risk factors and anticipate the likelihood of a difficult delivery of the fetal head at cesarean.

Options for managing an impacted fetal head at cesareanSeveral techniques have been reported in the literature for managing the delivery of a deeply engaged head, including:

Using an assistant to push the fetus’s head up using a hand in the vagina (“push” technique). This can cause trauma to the fetus, since the force required to push the fetus up from below is uncontrolled.^5,6

The reverse breech extraction (“pull” technique) involves pulling the infant out feet first through the uterine incision.⁷

Use of an instrument. The most common instrument used is a vacuum extractor,⁸ although a number of other devices have been developed, including the Murless fetal head extractor (an instrument with a hinged shaft and sliding collar lock),⁹ the C-Snorkel impacted fetal head release device (the device’s tip contains ventilation ports to facilitate airflow and release of the vacuum/suction created by the impacted fetal head),¹⁰ and the Fetal Pillow (a balloon device inserted in the vagina and inflated with sterile saline to disimpact an engaged fetal head before cesarean delivery).¹¹

While all of these techniques can cause injury to the mother and the fetus, available data favor use of the reverse breech extraction (pull) technique, since it is associated with fewer maternal risks, including lower rates of uterine incision extension, infection, and postpartum hemorrhage and a shorter operative time.¹²⁻¹⁸

Stop use of vacuum to deliver the fetal head at cesarean
Placement of a vacuum can be effective in assisting with delivery of the fetal head at cesarean. For this reason, vacuum-assisted deliveries at cesarean are becoming more common. While the rate of complications caused by vacuum extraction of the fetal head at cesarean is not known, injuries have been reported.^19,20 As such, routine use of vacuum extraction at the time of cesarean delivery cannot be recommended.

Start disengaging the fetal head prior to cesarean
One useful technique in planning a cesarean in the second stage of labor or when an impacted fetal head is anticipated is to disengage the fetal head vaginally prior to skin incision. This can be done in the delivery room or in the operating room immediately prior to surgery with the help of an assistant.

While supporting the patient’s legs, the assistant inserts a hand into the vagina and pushes upward on the fetal head with gentle, sustained effort. The assistant should use a cupped hand or the palm of the hand while attempting to both elevate and flex the fetal head. It is best to avoid using 1 or 2 fingers to elevate the head, as this may cause excessive pressure at a single point and lead to injury, such as a skull fracture (FIGURE). The assistant should disengage his or her hand only when the operating surgeon is able to reach down and secure the fetal head from above.

Elevating the fetal head prior to skin incision offers 3 major advantages:

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Rates of cesarean delivery in the second stage of labor have increased dramatically over the past few years.¹ Compared with cesarean delivery prior to labor, second-stage labor cesarean is associated with a higher risk to both the mother and the fetus; risks include excessive bleeding, lower uterine segment extensions, injuries to the maternal ureters or bladder, and injury to the fetus.²⁻⁴ The risk is increased even further if the fetal head is deeply impacted in the pelvis. What can we do to avoid and manage such situations?

Anticipate an impacted fetal headThe true incidence of an impacted fetal head at the time of cesarean is not known, although a number of risk factors have been described (TABLE). Obstetric care providers should be aware of these risk factors and anticipate the likelihood of a difficult delivery of the fetal head at cesarean.

Options for managing an impacted fetal head at cesareanSeveral techniques have been reported in the literature for managing the delivery of a deeply engaged head, including:

Using an assistant to push the fetus’s head up using a hand in the vagina (“push” technique). This can cause trauma to the fetus, since the force required to push the fetus up from below is uncontrolled.^5,6

The reverse breech extraction (“pull” technique) involves pulling the infant out feet first through the uterine incision.⁷

Use of an instrument. The most common instrument used is a vacuum extractor,⁸ although a number of other devices have been developed, including the Murless fetal head extractor (an instrument with a hinged shaft and sliding collar lock),⁹ the C-Snorkel impacted fetal head release device (the device’s tip contains ventilation ports to facilitate airflow and release of the vacuum/suction created by the impacted fetal head),¹⁰ and the Fetal Pillow (a balloon device inserted in the vagina and inflated with sterile saline to disimpact an engaged fetal head before cesarean delivery).¹¹

While all of these techniques can cause injury to the mother and the fetus, available data favor use of the reverse breech extraction (pull) technique, since it is associated with fewer maternal risks, including lower rates of uterine incision extension, infection, and postpartum hemorrhage and a shorter operative time.¹²⁻¹⁸

Stop use of vacuum to deliver the fetal head at cesarean
Placement of a vacuum can be effective in assisting with delivery of the fetal head at cesarean. For this reason, vacuum-assisted deliveries at cesarean are becoming more common. While the rate of complications caused by vacuum extraction of the fetal head at cesarean is not known, injuries have been reported.^19,20 As such, routine use of vacuum extraction at the time of cesarean delivery cannot be recommended.

Start disengaging the fetal head prior to cesarean
One useful technique in planning a cesarean in the second stage of labor or when an impacted fetal head is anticipated is to disengage the fetal head vaginally prior to skin incision. This can be done in the delivery room or in the operating room immediately prior to surgery with the help of an assistant.

While supporting the patient’s legs, the assistant inserts a hand into the vagina and pushes upward on the fetal head with gentle, sustained effort. The assistant should use a cupped hand or the palm of the hand while attempting to both elevate and flex the fetal head. It is best to avoid using 1 or 2 fingers to elevate the head, as this may cause excessive pressure at a single point and lead to injury, such as a skull fracture (FIGURE). The assistant should disengage his or her hand only when the operating surgeon is able to reach down and secure the fetal head from above.

Elevating the fetal head prior to skin incision offers 3 major advantages:

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Rates of cesarean delivery in the second stage of labor have increased dramatically over the past few years.¹ Compared with cesarean delivery prior to labor, second-stage labor cesarean is associated with a higher risk to both the mother and the fetus; risks include excessive bleeding, lower uterine segment extensions, injuries to the maternal ureters or bladder, and injury to the fetus.²⁻⁴ The risk is increased even further if the fetal head is deeply impacted in the pelvis. What can we do to avoid and manage such situations?

Anticipate an impacted fetal headThe true incidence of an impacted fetal head at the time of cesarean is not known, although a number of risk factors have been described (TABLE). Obstetric care providers should be aware of these risk factors and anticipate the likelihood of a difficult delivery of the fetal head at cesarean.

Options for managing an impacted fetal head at cesareanSeveral techniques have been reported in the literature for managing the delivery of a deeply engaged head, including:

Using an assistant to push the fetus’s head up using a hand in the vagina (“push” technique). This can cause trauma to the fetus, since the force required to push the fetus up from below is uncontrolled.^5,6

The reverse breech extraction (“pull” technique) involves pulling the infant out feet first through the uterine incision.⁷

Use of an instrument. The most common instrument used is a vacuum extractor,⁸ although a number of other devices have been developed, including the Murless fetal head extractor (an instrument with a hinged shaft and sliding collar lock),⁹ the C-Snorkel impacted fetal head release device (the device’s tip contains ventilation ports to facilitate airflow and release of the vacuum/suction created by the impacted fetal head),¹⁰ and the Fetal Pillow (a balloon device inserted in the vagina and inflated with sterile saline to disimpact an engaged fetal head before cesarean delivery).¹¹

While all of these techniques can cause injury to the mother and the fetus, available data favor use of the reverse breech extraction (pull) technique, since it is associated with fewer maternal risks, including lower rates of uterine incision extension, infection, and postpartum hemorrhage and a shorter operative time.¹²⁻¹⁸

Stop use of vacuum to deliver the fetal head at cesarean
Placement of a vacuum can be effective in assisting with delivery of the fetal head at cesarean. For this reason, vacuum-assisted deliveries at cesarean are becoming more common. While the rate of complications caused by vacuum extraction of the fetal head at cesarean is not known, injuries have been reported.^19,20 As such, routine use of vacuum extraction at the time of cesarean delivery cannot be recommended.

Start disengaging the fetal head prior to cesarean
One useful technique in planning a cesarean in the second stage of labor or when an impacted fetal head is anticipated is to disengage the fetal head vaginally prior to skin incision. This can be done in the delivery room or in the operating room immediately prior to surgery with the help of an assistant.

While supporting the patient’s legs, the assistant inserts a hand into the vagina and pushes upward on the fetal head with gentle, sustained effort. The assistant should use a cupped hand or the palm of the hand while attempting to both elevate and flex the fetal head. It is best to avoid using 1 or 2 fingers to elevate the head, as this may cause excessive pressure at a single point and lead to injury, such as a skull fracture (FIGURE). The assistant should disengage his or her hand only when the operating surgeon is able to reach down and secure the fetal head from above.

Elevating the fetal head prior to skin incision offers 3 major advantages:

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Since the current treatment choice for hormone-receptor–positive early breast cancer in postmenopausal women is 5 years of aromatase inhibitor (AI) therapy, or AI therapy following initial tamoxifen treatment, could 10 years of an AI be beneficial to cancer recurrence? Goss and colleagues analyzed this question in the MA.17R trial, a North American Breast Cancer Group trial coordinated by the Canadian Cancer Trials Group. (Results of the prior MA.17 trial were published in 2003.¹)

The randomized, double-blind, placebo-controlled trial evaluated the effect of 5 years of extended AI (letrozole 2.5 mg) treatment compared with placebo in menopausal women with hormone-receptor–positive breast cancer who had previously received 5 years of hormonal adjuvant therapy with tamoxifen alone or plus AIs. Of note, this study was funded in part by Novartis, the pharmaceutical manufacturer of letrozole, though the company had no role in either study design or writing of the manuscript. Seven of the 20 authors disclosed some sort of relationship with industry (some with the manufacturer of letrozole), including membership on advisory boards, board of directors, steering committees, or data and safety monitoring committees or receiving lecturer or consulting fees or grant support.

The trial’s primary end point was DFS. Secondary end points included overall survival, the incidence of contralateral breast cancer, quality of life (QOL), and long-term safety.

Details of the studyWomen were eligible to participate in the study if they were disease free after having completed 4.5 to 6 years of therapy with any AI and if their primary tumor was hormone-receptor positive. A total of 1,918 women were included in the trial and were randomly assigned to receive either letrozole treatment (n = 959) or placebo (n = 959).

Clinical evaluation was performed annually and included assessments of new bone fracture and new-onset osteoporosis, blood tests, mammography, and assessment of toxic effects. QOL measures were assessed with a validated health survey and a menopause-specific questionnaire. The Common Toxicity Criteria, version 2.0, was used to assess adverse events.

Impact on disease free, overall survivalThe rate of 5-year DFS was statistically improved in the letrozole group compared with the placebo group, 95% (95% confidence interval [CI], 93–96) versus 91% (95% CI, 89–93), respectively, a 4% improvement in DFS. However, there was no impact on disease-specific mortality and no benefit in overall survival (93% [95% CI, 92–95] with letrozole and 94% [95% CI, 92–95] with placebo), as competing causes of death become increasingly important in this older population. Among women who died during the study follow-up, more than half died of causes not related to breast cancer.

QOL measures. More than 85% of participants completed the QOL assessments at each time point. There was no difference in the various QOL measures between the letrozole and the placebo group.

Adverse effects. Expected adverse effects due to AIs were significantly higher in the letrozole group. For example, new-onset osteoporosis occurred in 109 (11%) of letrozole-treated women and in 54 (6%) of the placebo group (P<.001), and bone fracture occurred in 133 (14%) of the letrozole group and 88 (9%) of the placebo group (P = .001).

Of note, however, fewer toxicities/adverse effects were seen in the AI group in this study than in previously published reports. The authors suggested that these adverse effect data may be lower than expected because the majority of women eligible for this study likely had prior exposure to AIs, and those with significant adverse effects with aromatase inhibitor therapy may have self-selected out of this trial.

WHAT THIS EVIDENCE MEANS FOR PRACTICEWhile the study authors selected DFS as the primary outcome, the lack of overall survival, adverse effect profile, and the drug cost (average wholesale price, ~$33,050 for 5 years²) make the choice to routinely continue AIs in menopausal women with hormone-receptor–positive breast cancer less clear, and counseling on both the benefits and limitations of continuing hormonal adjuvant therapy will be important for these women.

Continued follow-up of the study participants over time would be useful to determine if, after 10 to 15 years, the benefit of extending AI therapy for an additional 5 years would provide an overall benefit in longevity, as competing causes of death (bone fracture, cardiovascular risk) actually may increase over time in the extended-treatment group compared with the placebo group.
— Mark D. Pearlman, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Since the current treatment choice for hormone-receptor–positive early breast cancer in postmenopausal women is 5 years of aromatase inhibitor (AI) therapy, or AI therapy following initial tamoxifen treatment, could 10 years of an AI be beneficial to cancer recurrence? Goss and colleagues analyzed this question in the MA.17R trial, a North American Breast Cancer Group trial coordinated by the Canadian Cancer Trials Group. (Results of the prior MA.17 trial were published in 2003.¹)

The randomized, double-blind, placebo-controlled trial evaluated the effect of 5 years of extended AI (letrozole 2.5 mg) treatment compared with placebo in menopausal women with hormone-receptor–positive breast cancer who had previously received 5 years of hormonal adjuvant therapy with tamoxifen alone or plus AIs. Of note, this study was funded in part by Novartis, the pharmaceutical manufacturer of letrozole, though the company had no role in either study design or writing of the manuscript. Seven of the 20 authors disclosed some sort of relationship with industry (some with the manufacturer of letrozole), including membership on advisory boards, board of directors, steering committees, or data and safety monitoring committees or receiving lecturer or consulting fees or grant support.

The trial’s primary end point was DFS. Secondary end points included overall survival, the incidence of contralateral breast cancer, quality of life (QOL), and long-term safety.

Details of the studyWomen were eligible to participate in the study if they were disease free after having completed 4.5 to 6 years of therapy with any AI and if their primary tumor was hormone-receptor positive. A total of 1,918 women were included in the trial and were randomly assigned to receive either letrozole treatment (n = 959) or placebo (n = 959).

Clinical evaluation was performed annually and included assessments of new bone fracture and new-onset osteoporosis, blood tests, mammography, and assessment of toxic effects. QOL measures were assessed with a validated health survey and a menopause-specific questionnaire. The Common Toxicity Criteria, version 2.0, was used to assess adverse events.

Impact on disease free, overall survivalThe rate of 5-year DFS was statistically improved in the letrozole group compared with the placebo group, 95% (95% confidence interval [CI], 93–96) versus 91% (95% CI, 89–93), respectively, a 4% improvement in DFS. However, there was no impact on disease-specific mortality and no benefit in overall survival (93% [95% CI, 92–95] with letrozole and 94% [95% CI, 92–95] with placebo), as competing causes of death become increasingly important in this older population. Among women who died during the study follow-up, more than half died of causes not related to breast cancer.

QOL measures. More than 85% of participants completed the QOL assessments at each time point. There was no difference in the various QOL measures between the letrozole and the placebo group.

Adverse effects. Expected adverse effects due to AIs were significantly higher in the letrozole group. For example, new-onset osteoporosis occurred in 109 (11%) of letrozole-treated women and in 54 (6%) of the placebo group (P<.001), and bone fracture occurred in 133 (14%) of the letrozole group and 88 (9%) of the placebo group (P = .001).

Of note, however, fewer toxicities/adverse effects were seen in the AI group in this study than in previously published reports. The authors suggested that these adverse effect data may be lower than expected because the majority of women eligible for this study likely had prior exposure to AIs, and those with significant adverse effects with aromatase inhibitor therapy may have self-selected out of this trial.

WHAT THIS EVIDENCE MEANS FOR PRACTICEWhile the study authors selected DFS as the primary outcome, the lack of overall survival, adverse effect profile, and the drug cost (average wholesale price, ~$33,050 for 5 years²) make the choice to routinely continue AIs in menopausal women with hormone-receptor–positive breast cancer less clear, and counseling on both the benefits and limitations of continuing hormonal adjuvant therapy will be important for these women.

Continued follow-up of the study participants over time would be useful to determine if, after 10 to 15 years, the benefit of extending AI therapy for an additional 5 years would provide an overall benefit in longevity, as competing causes of death (bone fracture, cardiovascular risk) actually may increase over time in the extended-treatment group compared with the placebo group.
— Mark D. Pearlman, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Since the current treatment choice for hormone-receptor–positive early breast cancer in postmenopausal women is 5 years of aromatase inhibitor (AI) therapy, or AI therapy following initial tamoxifen treatment, could 10 years of an AI be beneficial to cancer recurrence? Goss and colleagues analyzed this question in the MA.17R trial, a North American Breast Cancer Group trial coordinated by the Canadian Cancer Trials Group. (Results of the prior MA.17 trial were published in 2003.¹)

The randomized, double-blind, placebo-controlled trial evaluated the effect of 5 years of extended AI (letrozole 2.5 mg) treatment compared with placebo in menopausal women with hormone-receptor–positive breast cancer who had previously received 5 years of hormonal adjuvant therapy with tamoxifen alone or plus AIs. Of note, this study was funded in part by Novartis, the pharmaceutical manufacturer of letrozole, though the company had no role in either study design or writing of the manuscript. Seven of the 20 authors disclosed some sort of relationship with industry (some with the manufacturer of letrozole), including membership on advisory boards, board of directors, steering committees, or data and safety monitoring committees or receiving lecturer or consulting fees or grant support.

The trial’s primary end point was DFS. Secondary end points included overall survival, the incidence of contralateral breast cancer, quality of life (QOL), and long-term safety.

Details of the studyWomen were eligible to participate in the study if they were disease free after having completed 4.5 to 6 years of therapy with any AI and if their primary tumor was hormone-receptor positive. A total of 1,918 women were included in the trial and were randomly assigned to receive either letrozole treatment (n = 959) or placebo (n = 959).

Clinical evaluation was performed annually and included assessments of new bone fracture and new-onset osteoporosis, blood tests, mammography, and assessment of toxic effects. QOL measures were assessed with a validated health survey and a menopause-specific questionnaire. The Common Toxicity Criteria, version 2.0, was used to assess adverse events.

Impact on disease free, overall survivalThe rate of 5-year DFS was statistically improved in the letrozole group compared with the placebo group, 95% (95% confidence interval [CI], 93–96) versus 91% (95% CI, 89–93), respectively, a 4% improvement in DFS. However, there was no impact on disease-specific mortality and no benefit in overall survival (93% [95% CI, 92–95] with letrozole and 94% [95% CI, 92–95] with placebo), as competing causes of death become increasingly important in this older population. Among women who died during the study follow-up, more than half died of causes not related to breast cancer.

QOL measures. More than 85% of participants completed the QOL assessments at each time point. There was no difference in the various QOL measures between the letrozole and the placebo group.

Adverse effects. Expected adverse effects due to AIs were significantly higher in the letrozole group. For example, new-onset osteoporosis occurred in 109 (11%) of letrozole-treated women and in 54 (6%) of the placebo group (P<.001), and bone fracture occurred in 133 (14%) of the letrozole group and 88 (9%) of the placebo group (P = .001).

Of note, however, fewer toxicities/adverse effects were seen in the AI group in this study than in previously published reports. The authors suggested that these adverse effect data may be lower than expected because the majority of women eligible for this study likely had prior exposure to AIs, and those with significant adverse effects with aromatase inhibitor therapy may have self-selected out of this trial.

WHAT THIS EVIDENCE MEANS FOR PRACTICEWhile the study authors selected DFS as the primary outcome, the lack of overall survival, adverse effect profile, and the drug cost (average wholesale price, ~$33,050 for 5 years²) make the choice to routinely continue AIs in menopausal women with hormone-receptor–positive breast cancer less clear, and counseling on both the benefits and limitations of continuing hormonal adjuvant therapy will be important for these women.

Continued follow-up of the study participants over time would be useful to determine if, after 10 to 15 years, the benefit of extending AI therapy for an additional 5 years would provide an overall benefit in longevity, as competing causes of death (bone fracture, cardiovascular risk) actually may increase over time in the extended-treatment group compared with the placebo group.
— Mark D. Pearlman, MD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.